ckd 2016 100 1
TRANSCRIPT
Chronic Kidney DiseaseAn Update
(Part I)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Objectives
Upon completion of this talk the attendant will be able to
middot Understand the pathophysiology of Chronic Kidney Disease
middot Recognize the signs and symptoms of Chronic Kidney Disease
middot Identify the disease progression and treatment interventions
Plan
1-What is the definition and Epidemiology of Chronic Kidney Disease (CKD)
2-What is the Pathophysiology of CKD
3-How should clinicians estimate the stage of CKD
4-What laboratory tests and imaging should clinicians use to evaluate CKD
5-What clinical manifestations should clinicians look for when evaluating patients for CKD
6-How should clinicians construct a differential diagnosis of CKD
7-When should clinicians consider consulting with a nephrologist for diagnosing patients with possible CKD
8-How should Clinician Monitor CKD
9-Which drugs and other agents cause acute kidney injury in patients with CKD
Plan
What is the definition and Epidemiology of
Chronic Kidney Disease (CKD)
What is the definition of CKD
Structural or functional abnormalities of the kidneys for gt3 months as manifested by eithermiddot Kidney damage
middot Kidney damage can be either functional or structuralmiddot Functional abnormalities
middot Proteinuria albuminuriamiddot Abnormalities of urinary sediment (microscopic hematuria)
middot Structural abnormalitiesmiddot On ultrasound scanning or other radiological tests
(Polycystic kidney disease reflux nephropathy or other abnormalities)
middot The presence of GFR lt60 mLmin173 m2 for three months with or without other signs of kidney damage as described above
Am J Kidney Dis 2012 39S1
middot It is progressive tissue destruction with permanent loss of nephrons and renal function
middot CKD stage V eGFR lt 15 mlmin173 m2
middot ESRD is a defined term that indicates advanced CKD which necessitates treatment by Renal Replacement Therapy-RRT (dialysis ampor kidney transplantation)
What is the definition of CKD
CKD as a Public Health Issue
middot Increases risk for all-cause mortality
CV mortality
End stage renal disease (ESRD)
and other adverse outcomes
1 NKF Fact Sheets httpwwwkidneyorgnewsnewsroomfactsheetsFastFacts Accessed Nov 5 20142 USRDS wwwusrdsorg Accessed Nov 5 20143 Coresh et al JAMA 2007 2982038-2047
26 million Americans have CKD
Coresh et al 2015
Persistent albu-minuria with
eGFR ge 60
(CKD Stage I-II)
eGFR of 30-59 (CKD
Stage III)
eGFR of 15-29
(CKD Stage IV)
0
5
10
15
20
25
101
155
07
Mill
ions
of
peop
le
26 million American affectedPrevalence is 11-13 of adult population in the US
Data Source Special analyses Medicare 5 percent sample Known CKD stages presented as bars curve showing ldquoAll codesrdquo includes known CKD stages (codes 5851-5855) and the CKD-stage unspecified codes (5859 and remaining
non-585 CKD codes) Note In previous years this graph reported 5859 codes as a component of the stacked bars Abbreviation CKD chronic kidney disease
Trends in prevalence of recognized CKD overall
and by CKD stage among Medicare patients
aged 65+ 2000-2013
Stage I Stage II Stage III Stage IV Stage V
Chronic Kidney Disease (CKD)
USRDS ADR 2007
Prevalence of ESRD has been rising steadily
Prevalence of CKD by stage among NHANES
participants 1988-2012
Data Source National Health and Nutrition Examination Survey (NHANES) 1988ndash1994 1999-2004 amp 2007ndash2012 participants aged 20 amp older Whisker lines indicate 95 confidence intervals Abbreviations CKD chronic kidney disease
Incident ESRD patients rates adjusted for age amp gender
Incidence varies widely by race and ethnicity
Rate
per
mill
ion
popu
lati
on
Af Am
N AmHispanicAsian
WhiteNon-Hispanic
USRDS ADR 2007
Disproportionately affects African Americans and Hispanics
ESRD end stage renal disease USRDS ADR 2007
Diabetes and hypertension are leading causes of CKD
Incident ESRD rates by primary diagnosis adjusted for age gender amp race
USRDSIncident counts amp adjusted rates by age
USRDS ADR 2007
Prevalence of Abnormalities at each level of GFR
0102030405060708090
15-29 30-59 60-89 90+
Estimated GFR (mlmin173 m2)
Pro
porti
on o
f pop
ulat
ion
()
Hypertension Hemoglobin lt 120 gdLUnable to walk 14 mile Serum albumin lt 35 gdLSerum calcium lt 85 mgdL Serum phosphorus gt 45 mgdL
gt14090 or antihypertensive medication p-trend lt 0001 for each abnormality
Prevalence of CKD by age amp risk factor among
NHANES participants 1988-2012
Vol 1 CKD Ch 1 16
Data Source National Health and Nutrition Examination Survey (NHANES) 1988ndash1994 1999-2004 amp 2007ndash2012 participants aged 20 amp older Diabetes defined as either HbA1c gt7 self-reported or currently taking glucose-lowering medications Hypertension defined as BP ge130ge80 for those with diabetes or CKD otherwise BP ge140ge90 or taking medication for hypertension Abbreviations BMI body mass index CKD chronic kidney disease CVD cardiovascular disease DM diabetes mellitus HbA1c glycosylated hemoglobin HTN hypertension SR self-reported
CKD is disproportionately costly
Distribution of costs for CKD HTN amp diabetic patients in Medicare population 20014
Overall expenditures for CKD in the Medicare population age 65 amp older
Point prevalent Medicare CKD patients age 65 amp older costs are total expenditures per calendar year28 of Medicare budget in 2013 up from 69 in 1993
($42 billion in 2013)
USRDS ADR 2013
Data Source Special analyses Medicare 5 percent sample Abbreviations CKD chronic kidney disease CHF congestive heart failure DM diabetes mellitus PPPY per person per year
Per person per year expenditures on Parts A B and D
services for the CKD Medicare population aged 65+ by
DM CHF and year 1993-2013
Per person per month (PPPM) expenditures during the transition to ESRD by dataset 2011
Incident Medicare (age 67 amp older) amp Truven Health MarketScan (younger than 65) ESRD patients initiating in 2008
USRDS ADR 2013
Preventing progression of CKD will help hold
down costs as the treatment of ESRD is expensive requires
some type of replacement therapy
to maintain life
Relationships between cardiac events and loss of life expectancy resulting from CVD by stage of CKD
Marcello Tonelli et al Circulation 2016133518-536The Lancet Gansevoort et al 2013 Elsevier
Data source Special analyses Medicare 5 percent sample January 1 of each reported year point prevalent Medicare patients age 66 and older Ref 2012 patients Abbreviation CKD chronic kidney disease
All-cause mortality rates (per 1000 patient years at
risk) for Medicare patients aged 66+ by CKD status
and year 2001-2013
Data source Special analyses Medicare 5 percent sample January 1 2013 point prevalent patients aged 66 and older Adj agesexrace Ref all patients 2013 Abbreviations CKD chronic kidney disease CVD
cardiovascular disease DM diabetes mellitus
Adjusted all-cause mortality rates (per 1000 patient years at risk) for Medicare patients aged 66+ by cardiovascular disease and diabetes mellitus CKD status and stage 2013
Cardiovascular Mortality in the General Population and in ESRD Treated by Dialysis
001
100
10
1
01
Annual mortality ()
25ndash34 45ndash54 65ndash74 8535ndash44 55ndash64 75ndash84
MaleFemaleBlackWhite
Dialysis
General population
Age (years)
Am J Kidney Dis 2012 39(S2) S1-246
Data Source National Health and Nutrition Examination Survey (NHANES) 2001-2012 participants aged 20 amp older Abbreviations CKD chronic kidney disease
NHANES participants with CKD aware of their
kidney disease 2001-2012
Gaps in CKD Diagnosis In Diabetic Patients
Szczech Lynda A et al Primary Care Detection of Chronic Kidney Disease in Adults with Type-2 Diabetes The ADD-CKD Study (Awareness Detection and Drug Therapy in Type-2 Diabetes and Chronic Kidney Disease) PLOS One - In press (2014)
0204060
CKD Screening in Primary Care( of patients)
of Patients
Improved Diagnosis of CKDIn Diabetic Patients
Studies demonstrate that clinician behavior changes when CKD diagnosis improves Significant improvements realized in1-3
bull Increased urinary albumin testing
bull Increased appropriate use of ACEi or ARBs
bull Avoidance of NSAIDs prescribing among patients with low proteinuria ampor eGFR
bull Appropriate nephrology consultation
1 Wei L et al Kidney Int 201384174-1782 Chan M et al Am J Med 20071201063-10703 Fink J et al Am J Kidney Dis 200953681-668
Plan
What is the Pathophysiology of CKD
Pathophysiology of CKD
Risk Factors and Causes for CKD
Pathophysiology of CKD
Stage I amp II CKDDiminished Renal Reserve
eGFR 50
eGFR
Proteinuria
Glomerulosclerosis
ImpairedSluggish Blood Flow
Modifiable Factors-DM-Hypertension-Increase Protein amp Fat intake-Smoking-Use of NSAIDS
Non-Modifiable Factors-Heriditary-Age greater than 60 yrs old-Gender-Race
Thickening ampor an in the amount of collagen in the
basement membranes of the small vessels
Pathophysiology of CKD
Pathophysiological Events Underlying the Origin and Evolution of Hypertensive Nephropathy
Pathogenesis of kidney disease in patients with diabetes
Muskiet M H A et al (2013) Nat Rev Nephrol doi101038nrneph2013272
Pathophysiology of CKD
Pathophysiology of CKD
Pathogenesis of disordered mineral metabolism in CKD
Increase FGF-23
Hypocalcemia
Increase PTH
Bone Disease
Severe inhibition of 1-α hydroxylase and
125 dihydroxyvitamin D
Vit D DeficiencyVit D Resistance
Hyperphosphatemia
Decrease GFR
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Objectives
Upon completion of this talk the attendant will be able to
middot Understand the pathophysiology of Chronic Kidney Disease
middot Recognize the signs and symptoms of Chronic Kidney Disease
middot Identify the disease progression and treatment interventions
Plan
1-What is the definition and Epidemiology of Chronic Kidney Disease (CKD)
2-What is the Pathophysiology of CKD
3-How should clinicians estimate the stage of CKD
4-What laboratory tests and imaging should clinicians use to evaluate CKD
5-What clinical manifestations should clinicians look for when evaluating patients for CKD
6-How should clinicians construct a differential diagnosis of CKD
7-When should clinicians consider consulting with a nephrologist for diagnosing patients with possible CKD
8-How should Clinician Monitor CKD
9-Which drugs and other agents cause acute kidney injury in patients with CKD
Plan
What is the definition and Epidemiology of
Chronic Kidney Disease (CKD)
What is the definition of CKD
Structural or functional abnormalities of the kidneys for gt3 months as manifested by eithermiddot Kidney damage
middot Kidney damage can be either functional or structuralmiddot Functional abnormalities
middot Proteinuria albuminuriamiddot Abnormalities of urinary sediment (microscopic hematuria)
middot Structural abnormalitiesmiddot On ultrasound scanning or other radiological tests
(Polycystic kidney disease reflux nephropathy or other abnormalities)
middot The presence of GFR lt60 mLmin173 m2 for three months with or without other signs of kidney damage as described above
Am J Kidney Dis 2012 39S1
middot It is progressive tissue destruction with permanent loss of nephrons and renal function
middot CKD stage V eGFR lt 15 mlmin173 m2
middot ESRD is a defined term that indicates advanced CKD which necessitates treatment by Renal Replacement Therapy-RRT (dialysis ampor kidney transplantation)
What is the definition of CKD
CKD as a Public Health Issue
middot Increases risk for all-cause mortality
CV mortality
End stage renal disease (ESRD)
and other adverse outcomes
1 NKF Fact Sheets httpwwwkidneyorgnewsnewsroomfactsheetsFastFacts Accessed Nov 5 20142 USRDS wwwusrdsorg Accessed Nov 5 20143 Coresh et al JAMA 2007 2982038-2047
26 million Americans have CKD
Coresh et al 2015
Persistent albu-minuria with
eGFR ge 60
(CKD Stage I-II)
eGFR of 30-59 (CKD
Stage III)
eGFR of 15-29
(CKD Stage IV)
0
5
10
15
20
25
101
155
07
Mill
ions
of
peop
le
26 million American affectedPrevalence is 11-13 of adult population in the US
Data Source Special analyses Medicare 5 percent sample Known CKD stages presented as bars curve showing ldquoAll codesrdquo includes known CKD stages (codes 5851-5855) and the CKD-stage unspecified codes (5859 and remaining
non-585 CKD codes) Note In previous years this graph reported 5859 codes as a component of the stacked bars Abbreviation CKD chronic kidney disease
Trends in prevalence of recognized CKD overall
and by CKD stage among Medicare patients
aged 65+ 2000-2013
Stage I Stage II Stage III Stage IV Stage V
Chronic Kidney Disease (CKD)
USRDS ADR 2007
Prevalence of ESRD has been rising steadily
Prevalence of CKD by stage among NHANES
participants 1988-2012
Data Source National Health and Nutrition Examination Survey (NHANES) 1988ndash1994 1999-2004 amp 2007ndash2012 participants aged 20 amp older Whisker lines indicate 95 confidence intervals Abbreviations CKD chronic kidney disease
Incident ESRD patients rates adjusted for age amp gender
Incidence varies widely by race and ethnicity
Rate
per
mill
ion
popu
lati
on
Af Am
N AmHispanicAsian
WhiteNon-Hispanic
USRDS ADR 2007
Disproportionately affects African Americans and Hispanics
ESRD end stage renal disease USRDS ADR 2007
Diabetes and hypertension are leading causes of CKD
Incident ESRD rates by primary diagnosis adjusted for age gender amp race
USRDSIncident counts amp adjusted rates by age
USRDS ADR 2007
Prevalence of Abnormalities at each level of GFR
0102030405060708090
15-29 30-59 60-89 90+
Estimated GFR (mlmin173 m2)
Pro
porti
on o
f pop
ulat
ion
()
Hypertension Hemoglobin lt 120 gdLUnable to walk 14 mile Serum albumin lt 35 gdLSerum calcium lt 85 mgdL Serum phosphorus gt 45 mgdL
gt14090 or antihypertensive medication p-trend lt 0001 for each abnormality
Prevalence of CKD by age amp risk factor among
NHANES participants 1988-2012
Vol 1 CKD Ch 1 16
Data Source National Health and Nutrition Examination Survey (NHANES) 1988ndash1994 1999-2004 amp 2007ndash2012 participants aged 20 amp older Diabetes defined as either HbA1c gt7 self-reported or currently taking glucose-lowering medications Hypertension defined as BP ge130ge80 for those with diabetes or CKD otherwise BP ge140ge90 or taking medication for hypertension Abbreviations BMI body mass index CKD chronic kidney disease CVD cardiovascular disease DM diabetes mellitus HbA1c glycosylated hemoglobin HTN hypertension SR self-reported
CKD is disproportionately costly
Distribution of costs for CKD HTN amp diabetic patients in Medicare population 20014
Overall expenditures for CKD in the Medicare population age 65 amp older
Point prevalent Medicare CKD patients age 65 amp older costs are total expenditures per calendar year28 of Medicare budget in 2013 up from 69 in 1993
($42 billion in 2013)
USRDS ADR 2013
Data Source Special analyses Medicare 5 percent sample Abbreviations CKD chronic kidney disease CHF congestive heart failure DM diabetes mellitus PPPY per person per year
Per person per year expenditures on Parts A B and D
services for the CKD Medicare population aged 65+ by
DM CHF and year 1993-2013
Per person per month (PPPM) expenditures during the transition to ESRD by dataset 2011
Incident Medicare (age 67 amp older) amp Truven Health MarketScan (younger than 65) ESRD patients initiating in 2008
USRDS ADR 2013
Preventing progression of CKD will help hold
down costs as the treatment of ESRD is expensive requires
some type of replacement therapy
to maintain life
Relationships between cardiac events and loss of life expectancy resulting from CVD by stage of CKD
Marcello Tonelli et al Circulation 2016133518-536The Lancet Gansevoort et al 2013 Elsevier
Data source Special analyses Medicare 5 percent sample January 1 of each reported year point prevalent Medicare patients age 66 and older Ref 2012 patients Abbreviation CKD chronic kidney disease
All-cause mortality rates (per 1000 patient years at
risk) for Medicare patients aged 66+ by CKD status
and year 2001-2013
Data source Special analyses Medicare 5 percent sample January 1 2013 point prevalent patients aged 66 and older Adj agesexrace Ref all patients 2013 Abbreviations CKD chronic kidney disease CVD
cardiovascular disease DM diabetes mellitus
Adjusted all-cause mortality rates (per 1000 patient years at risk) for Medicare patients aged 66+ by cardiovascular disease and diabetes mellitus CKD status and stage 2013
Cardiovascular Mortality in the General Population and in ESRD Treated by Dialysis
001
100
10
1
01
Annual mortality ()
25ndash34 45ndash54 65ndash74 8535ndash44 55ndash64 75ndash84
MaleFemaleBlackWhite
Dialysis
General population
Age (years)
Am J Kidney Dis 2012 39(S2) S1-246
Data Source National Health and Nutrition Examination Survey (NHANES) 2001-2012 participants aged 20 amp older Abbreviations CKD chronic kidney disease
NHANES participants with CKD aware of their
kidney disease 2001-2012
Gaps in CKD Diagnosis In Diabetic Patients
Szczech Lynda A et al Primary Care Detection of Chronic Kidney Disease in Adults with Type-2 Diabetes The ADD-CKD Study (Awareness Detection and Drug Therapy in Type-2 Diabetes and Chronic Kidney Disease) PLOS One - In press (2014)
0204060
CKD Screening in Primary Care( of patients)
of Patients
Improved Diagnosis of CKDIn Diabetic Patients
Studies demonstrate that clinician behavior changes when CKD diagnosis improves Significant improvements realized in1-3
bull Increased urinary albumin testing
bull Increased appropriate use of ACEi or ARBs
bull Avoidance of NSAIDs prescribing among patients with low proteinuria ampor eGFR
bull Appropriate nephrology consultation
1 Wei L et al Kidney Int 201384174-1782 Chan M et al Am J Med 20071201063-10703 Fink J et al Am J Kidney Dis 200953681-668
Plan
What is the Pathophysiology of CKD
Pathophysiology of CKD
Risk Factors and Causes for CKD
Pathophysiology of CKD
Stage I amp II CKDDiminished Renal Reserve
eGFR 50
eGFR
Proteinuria
Glomerulosclerosis
ImpairedSluggish Blood Flow
Modifiable Factors-DM-Hypertension-Increase Protein amp Fat intake-Smoking-Use of NSAIDS
Non-Modifiable Factors-Heriditary-Age greater than 60 yrs old-Gender-Race
Thickening ampor an in the amount of collagen in the
basement membranes of the small vessels
Pathophysiology of CKD
Pathophysiological Events Underlying the Origin and Evolution of Hypertensive Nephropathy
Pathogenesis of kidney disease in patients with diabetes
Muskiet M H A et al (2013) Nat Rev Nephrol doi101038nrneph2013272
Pathophysiology of CKD
Pathophysiology of CKD
Pathogenesis of disordered mineral metabolism in CKD
Increase FGF-23
Hypocalcemia
Increase PTH
Bone Disease
Severe inhibition of 1-α hydroxylase and
125 dihydroxyvitamin D
Vit D DeficiencyVit D Resistance
Hyperphosphatemia
Decrease GFR
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Plan
1-What is the definition and Epidemiology of Chronic Kidney Disease (CKD)
2-What is the Pathophysiology of CKD
3-How should clinicians estimate the stage of CKD
4-What laboratory tests and imaging should clinicians use to evaluate CKD
5-What clinical manifestations should clinicians look for when evaluating patients for CKD
6-How should clinicians construct a differential diagnosis of CKD
7-When should clinicians consider consulting with a nephrologist for diagnosing patients with possible CKD
8-How should Clinician Monitor CKD
9-Which drugs and other agents cause acute kidney injury in patients with CKD
Plan
What is the definition and Epidemiology of
Chronic Kidney Disease (CKD)
What is the definition of CKD
Structural or functional abnormalities of the kidneys for gt3 months as manifested by eithermiddot Kidney damage
middot Kidney damage can be either functional or structuralmiddot Functional abnormalities
middot Proteinuria albuminuriamiddot Abnormalities of urinary sediment (microscopic hematuria)
middot Structural abnormalitiesmiddot On ultrasound scanning or other radiological tests
(Polycystic kidney disease reflux nephropathy or other abnormalities)
middot The presence of GFR lt60 mLmin173 m2 for three months with or without other signs of kidney damage as described above
Am J Kidney Dis 2012 39S1
middot It is progressive tissue destruction with permanent loss of nephrons and renal function
middot CKD stage V eGFR lt 15 mlmin173 m2
middot ESRD is a defined term that indicates advanced CKD which necessitates treatment by Renal Replacement Therapy-RRT (dialysis ampor kidney transplantation)
What is the definition of CKD
CKD as a Public Health Issue
middot Increases risk for all-cause mortality
CV mortality
End stage renal disease (ESRD)
and other adverse outcomes
1 NKF Fact Sheets httpwwwkidneyorgnewsnewsroomfactsheetsFastFacts Accessed Nov 5 20142 USRDS wwwusrdsorg Accessed Nov 5 20143 Coresh et al JAMA 2007 2982038-2047
26 million Americans have CKD
Coresh et al 2015
Persistent albu-minuria with
eGFR ge 60
(CKD Stage I-II)
eGFR of 30-59 (CKD
Stage III)
eGFR of 15-29
(CKD Stage IV)
0
5
10
15
20
25
101
155
07
Mill
ions
of
peop
le
26 million American affectedPrevalence is 11-13 of adult population in the US
Data Source Special analyses Medicare 5 percent sample Known CKD stages presented as bars curve showing ldquoAll codesrdquo includes known CKD stages (codes 5851-5855) and the CKD-stage unspecified codes (5859 and remaining
non-585 CKD codes) Note In previous years this graph reported 5859 codes as a component of the stacked bars Abbreviation CKD chronic kidney disease
Trends in prevalence of recognized CKD overall
and by CKD stage among Medicare patients
aged 65+ 2000-2013
Stage I Stage II Stage III Stage IV Stage V
Chronic Kidney Disease (CKD)
USRDS ADR 2007
Prevalence of ESRD has been rising steadily
Prevalence of CKD by stage among NHANES
participants 1988-2012
Data Source National Health and Nutrition Examination Survey (NHANES) 1988ndash1994 1999-2004 amp 2007ndash2012 participants aged 20 amp older Whisker lines indicate 95 confidence intervals Abbreviations CKD chronic kidney disease
Incident ESRD patients rates adjusted for age amp gender
Incidence varies widely by race and ethnicity
Rate
per
mill
ion
popu
lati
on
Af Am
N AmHispanicAsian
WhiteNon-Hispanic
USRDS ADR 2007
Disproportionately affects African Americans and Hispanics
ESRD end stage renal disease USRDS ADR 2007
Diabetes and hypertension are leading causes of CKD
Incident ESRD rates by primary diagnosis adjusted for age gender amp race
USRDSIncident counts amp adjusted rates by age
USRDS ADR 2007
Prevalence of Abnormalities at each level of GFR
0102030405060708090
15-29 30-59 60-89 90+
Estimated GFR (mlmin173 m2)
Pro
porti
on o
f pop
ulat
ion
()
Hypertension Hemoglobin lt 120 gdLUnable to walk 14 mile Serum albumin lt 35 gdLSerum calcium lt 85 mgdL Serum phosphorus gt 45 mgdL
gt14090 or antihypertensive medication p-trend lt 0001 for each abnormality
Prevalence of CKD by age amp risk factor among
NHANES participants 1988-2012
Vol 1 CKD Ch 1 16
Data Source National Health and Nutrition Examination Survey (NHANES) 1988ndash1994 1999-2004 amp 2007ndash2012 participants aged 20 amp older Diabetes defined as either HbA1c gt7 self-reported or currently taking glucose-lowering medications Hypertension defined as BP ge130ge80 for those with diabetes or CKD otherwise BP ge140ge90 or taking medication for hypertension Abbreviations BMI body mass index CKD chronic kidney disease CVD cardiovascular disease DM diabetes mellitus HbA1c glycosylated hemoglobin HTN hypertension SR self-reported
CKD is disproportionately costly
Distribution of costs for CKD HTN amp diabetic patients in Medicare population 20014
Overall expenditures for CKD in the Medicare population age 65 amp older
Point prevalent Medicare CKD patients age 65 amp older costs are total expenditures per calendar year28 of Medicare budget in 2013 up from 69 in 1993
($42 billion in 2013)
USRDS ADR 2013
Data Source Special analyses Medicare 5 percent sample Abbreviations CKD chronic kidney disease CHF congestive heart failure DM diabetes mellitus PPPY per person per year
Per person per year expenditures on Parts A B and D
services for the CKD Medicare population aged 65+ by
DM CHF and year 1993-2013
Per person per month (PPPM) expenditures during the transition to ESRD by dataset 2011
Incident Medicare (age 67 amp older) amp Truven Health MarketScan (younger than 65) ESRD patients initiating in 2008
USRDS ADR 2013
Preventing progression of CKD will help hold
down costs as the treatment of ESRD is expensive requires
some type of replacement therapy
to maintain life
Relationships between cardiac events and loss of life expectancy resulting from CVD by stage of CKD
Marcello Tonelli et al Circulation 2016133518-536The Lancet Gansevoort et al 2013 Elsevier
Data source Special analyses Medicare 5 percent sample January 1 of each reported year point prevalent Medicare patients age 66 and older Ref 2012 patients Abbreviation CKD chronic kidney disease
All-cause mortality rates (per 1000 patient years at
risk) for Medicare patients aged 66+ by CKD status
and year 2001-2013
Data source Special analyses Medicare 5 percent sample January 1 2013 point prevalent patients aged 66 and older Adj agesexrace Ref all patients 2013 Abbreviations CKD chronic kidney disease CVD
cardiovascular disease DM diabetes mellitus
Adjusted all-cause mortality rates (per 1000 patient years at risk) for Medicare patients aged 66+ by cardiovascular disease and diabetes mellitus CKD status and stage 2013
Cardiovascular Mortality in the General Population and in ESRD Treated by Dialysis
001
100
10
1
01
Annual mortality ()
25ndash34 45ndash54 65ndash74 8535ndash44 55ndash64 75ndash84
MaleFemaleBlackWhite
Dialysis
General population
Age (years)
Am J Kidney Dis 2012 39(S2) S1-246
Data Source National Health and Nutrition Examination Survey (NHANES) 2001-2012 participants aged 20 amp older Abbreviations CKD chronic kidney disease
NHANES participants with CKD aware of their
kidney disease 2001-2012
Gaps in CKD Diagnosis In Diabetic Patients
Szczech Lynda A et al Primary Care Detection of Chronic Kidney Disease in Adults with Type-2 Diabetes The ADD-CKD Study (Awareness Detection and Drug Therapy in Type-2 Diabetes and Chronic Kidney Disease) PLOS One - In press (2014)
0204060
CKD Screening in Primary Care( of patients)
of Patients
Improved Diagnosis of CKDIn Diabetic Patients
Studies demonstrate that clinician behavior changes when CKD diagnosis improves Significant improvements realized in1-3
bull Increased urinary albumin testing
bull Increased appropriate use of ACEi or ARBs
bull Avoidance of NSAIDs prescribing among patients with low proteinuria ampor eGFR
bull Appropriate nephrology consultation
1 Wei L et al Kidney Int 201384174-1782 Chan M et al Am J Med 20071201063-10703 Fink J et al Am J Kidney Dis 200953681-668
Plan
What is the Pathophysiology of CKD
Pathophysiology of CKD
Risk Factors and Causes for CKD
Pathophysiology of CKD
Stage I amp II CKDDiminished Renal Reserve
eGFR 50
eGFR
Proteinuria
Glomerulosclerosis
ImpairedSluggish Blood Flow
Modifiable Factors-DM-Hypertension-Increase Protein amp Fat intake-Smoking-Use of NSAIDS
Non-Modifiable Factors-Heriditary-Age greater than 60 yrs old-Gender-Race
Thickening ampor an in the amount of collagen in the
basement membranes of the small vessels
Pathophysiology of CKD
Pathophysiological Events Underlying the Origin and Evolution of Hypertensive Nephropathy
Pathogenesis of kidney disease in patients with diabetes
Muskiet M H A et al (2013) Nat Rev Nephrol doi101038nrneph2013272
Pathophysiology of CKD
Pathophysiology of CKD
Pathogenesis of disordered mineral metabolism in CKD
Increase FGF-23
Hypocalcemia
Increase PTH
Bone Disease
Severe inhibition of 1-α hydroxylase and
125 dihydroxyvitamin D
Vit D DeficiencyVit D Resistance
Hyperphosphatemia
Decrease GFR
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Plan
What is the definition and Epidemiology of
Chronic Kidney Disease (CKD)
What is the definition of CKD
Structural or functional abnormalities of the kidneys for gt3 months as manifested by eithermiddot Kidney damage
middot Kidney damage can be either functional or structuralmiddot Functional abnormalities
middot Proteinuria albuminuriamiddot Abnormalities of urinary sediment (microscopic hematuria)
middot Structural abnormalitiesmiddot On ultrasound scanning or other radiological tests
(Polycystic kidney disease reflux nephropathy or other abnormalities)
middot The presence of GFR lt60 mLmin173 m2 for three months with or without other signs of kidney damage as described above
Am J Kidney Dis 2012 39S1
middot It is progressive tissue destruction with permanent loss of nephrons and renal function
middot CKD stage V eGFR lt 15 mlmin173 m2
middot ESRD is a defined term that indicates advanced CKD which necessitates treatment by Renal Replacement Therapy-RRT (dialysis ampor kidney transplantation)
What is the definition of CKD
CKD as a Public Health Issue
middot Increases risk for all-cause mortality
CV mortality
End stage renal disease (ESRD)
and other adverse outcomes
1 NKF Fact Sheets httpwwwkidneyorgnewsnewsroomfactsheetsFastFacts Accessed Nov 5 20142 USRDS wwwusrdsorg Accessed Nov 5 20143 Coresh et al JAMA 2007 2982038-2047
26 million Americans have CKD
Coresh et al 2015
Persistent albu-minuria with
eGFR ge 60
(CKD Stage I-II)
eGFR of 30-59 (CKD
Stage III)
eGFR of 15-29
(CKD Stage IV)
0
5
10
15
20
25
101
155
07
Mill
ions
of
peop
le
26 million American affectedPrevalence is 11-13 of adult population in the US
Data Source Special analyses Medicare 5 percent sample Known CKD stages presented as bars curve showing ldquoAll codesrdquo includes known CKD stages (codes 5851-5855) and the CKD-stage unspecified codes (5859 and remaining
non-585 CKD codes) Note In previous years this graph reported 5859 codes as a component of the stacked bars Abbreviation CKD chronic kidney disease
Trends in prevalence of recognized CKD overall
and by CKD stage among Medicare patients
aged 65+ 2000-2013
Stage I Stage II Stage III Stage IV Stage V
Chronic Kidney Disease (CKD)
USRDS ADR 2007
Prevalence of ESRD has been rising steadily
Prevalence of CKD by stage among NHANES
participants 1988-2012
Data Source National Health and Nutrition Examination Survey (NHANES) 1988ndash1994 1999-2004 amp 2007ndash2012 participants aged 20 amp older Whisker lines indicate 95 confidence intervals Abbreviations CKD chronic kidney disease
Incident ESRD patients rates adjusted for age amp gender
Incidence varies widely by race and ethnicity
Rate
per
mill
ion
popu
lati
on
Af Am
N AmHispanicAsian
WhiteNon-Hispanic
USRDS ADR 2007
Disproportionately affects African Americans and Hispanics
ESRD end stage renal disease USRDS ADR 2007
Diabetes and hypertension are leading causes of CKD
Incident ESRD rates by primary diagnosis adjusted for age gender amp race
USRDSIncident counts amp adjusted rates by age
USRDS ADR 2007
Prevalence of Abnormalities at each level of GFR
0102030405060708090
15-29 30-59 60-89 90+
Estimated GFR (mlmin173 m2)
Pro
porti
on o
f pop
ulat
ion
()
Hypertension Hemoglobin lt 120 gdLUnable to walk 14 mile Serum albumin lt 35 gdLSerum calcium lt 85 mgdL Serum phosphorus gt 45 mgdL
gt14090 or antihypertensive medication p-trend lt 0001 for each abnormality
Prevalence of CKD by age amp risk factor among
NHANES participants 1988-2012
Vol 1 CKD Ch 1 16
Data Source National Health and Nutrition Examination Survey (NHANES) 1988ndash1994 1999-2004 amp 2007ndash2012 participants aged 20 amp older Diabetes defined as either HbA1c gt7 self-reported or currently taking glucose-lowering medications Hypertension defined as BP ge130ge80 for those with diabetes or CKD otherwise BP ge140ge90 or taking medication for hypertension Abbreviations BMI body mass index CKD chronic kidney disease CVD cardiovascular disease DM diabetes mellitus HbA1c glycosylated hemoglobin HTN hypertension SR self-reported
CKD is disproportionately costly
Distribution of costs for CKD HTN amp diabetic patients in Medicare population 20014
Overall expenditures for CKD in the Medicare population age 65 amp older
Point prevalent Medicare CKD patients age 65 amp older costs are total expenditures per calendar year28 of Medicare budget in 2013 up from 69 in 1993
($42 billion in 2013)
USRDS ADR 2013
Data Source Special analyses Medicare 5 percent sample Abbreviations CKD chronic kidney disease CHF congestive heart failure DM diabetes mellitus PPPY per person per year
Per person per year expenditures on Parts A B and D
services for the CKD Medicare population aged 65+ by
DM CHF and year 1993-2013
Per person per month (PPPM) expenditures during the transition to ESRD by dataset 2011
Incident Medicare (age 67 amp older) amp Truven Health MarketScan (younger than 65) ESRD patients initiating in 2008
USRDS ADR 2013
Preventing progression of CKD will help hold
down costs as the treatment of ESRD is expensive requires
some type of replacement therapy
to maintain life
Relationships between cardiac events and loss of life expectancy resulting from CVD by stage of CKD
Marcello Tonelli et al Circulation 2016133518-536The Lancet Gansevoort et al 2013 Elsevier
Data source Special analyses Medicare 5 percent sample January 1 of each reported year point prevalent Medicare patients age 66 and older Ref 2012 patients Abbreviation CKD chronic kidney disease
All-cause mortality rates (per 1000 patient years at
risk) for Medicare patients aged 66+ by CKD status
and year 2001-2013
Data source Special analyses Medicare 5 percent sample January 1 2013 point prevalent patients aged 66 and older Adj agesexrace Ref all patients 2013 Abbreviations CKD chronic kidney disease CVD
cardiovascular disease DM diabetes mellitus
Adjusted all-cause mortality rates (per 1000 patient years at risk) for Medicare patients aged 66+ by cardiovascular disease and diabetes mellitus CKD status and stage 2013
Cardiovascular Mortality in the General Population and in ESRD Treated by Dialysis
001
100
10
1
01
Annual mortality ()
25ndash34 45ndash54 65ndash74 8535ndash44 55ndash64 75ndash84
MaleFemaleBlackWhite
Dialysis
General population
Age (years)
Am J Kidney Dis 2012 39(S2) S1-246
Data Source National Health and Nutrition Examination Survey (NHANES) 2001-2012 participants aged 20 amp older Abbreviations CKD chronic kidney disease
NHANES participants with CKD aware of their
kidney disease 2001-2012
Gaps in CKD Diagnosis In Diabetic Patients
Szczech Lynda A et al Primary Care Detection of Chronic Kidney Disease in Adults with Type-2 Diabetes The ADD-CKD Study (Awareness Detection and Drug Therapy in Type-2 Diabetes and Chronic Kidney Disease) PLOS One - In press (2014)
0204060
CKD Screening in Primary Care( of patients)
of Patients
Improved Diagnosis of CKDIn Diabetic Patients
Studies demonstrate that clinician behavior changes when CKD diagnosis improves Significant improvements realized in1-3
bull Increased urinary albumin testing
bull Increased appropriate use of ACEi or ARBs
bull Avoidance of NSAIDs prescribing among patients with low proteinuria ampor eGFR
bull Appropriate nephrology consultation
1 Wei L et al Kidney Int 201384174-1782 Chan M et al Am J Med 20071201063-10703 Fink J et al Am J Kidney Dis 200953681-668
Plan
What is the Pathophysiology of CKD
Pathophysiology of CKD
Risk Factors and Causes for CKD
Pathophysiology of CKD
Stage I amp II CKDDiminished Renal Reserve
eGFR 50
eGFR
Proteinuria
Glomerulosclerosis
ImpairedSluggish Blood Flow
Modifiable Factors-DM-Hypertension-Increase Protein amp Fat intake-Smoking-Use of NSAIDS
Non-Modifiable Factors-Heriditary-Age greater than 60 yrs old-Gender-Race
Thickening ampor an in the amount of collagen in the
basement membranes of the small vessels
Pathophysiology of CKD
Pathophysiological Events Underlying the Origin and Evolution of Hypertensive Nephropathy
Pathogenesis of kidney disease in patients with diabetes
Muskiet M H A et al (2013) Nat Rev Nephrol doi101038nrneph2013272
Pathophysiology of CKD
Pathophysiology of CKD
Pathogenesis of disordered mineral metabolism in CKD
Increase FGF-23
Hypocalcemia
Increase PTH
Bone Disease
Severe inhibition of 1-α hydroxylase and
125 dihydroxyvitamin D
Vit D DeficiencyVit D Resistance
Hyperphosphatemia
Decrease GFR
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
What is the definition of CKD
Structural or functional abnormalities of the kidneys for gt3 months as manifested by eithermiddot Kidney damage
middot Kidney damage can be either functional or structuralmiddot Functional abnormalities
middot Proteinuria albuminuriamiddot Abnormalities of urinary sediment (microscopic hematuria)
middot Structural abnormalitiesmiddot On ultrasound scanning or other radiological tests
(Polycystic kidney disease reflux nephropathy or other abnormalities)
middot The presence of GFR lt60 mLmin173 m2 for three months with or without other signs of kidney damage as described above
Am J Kidney Dis 2012 39S1
middot It is progressive tissue destruction with permanent loss of nephrons and renal function
middot CKD stage V eGFR lt 15 mlmin173 m2
middot ESRD is a defined term that indicates advanced CKD which necessitates treatment by Renal Replacement Therapy-RRT (dialysis ampor kidney transplantation)
What is the definition of CKD
CKD as a Public Health Issue
middot Increases risk for all-cause mortality
CV mortality
End stage renal disease (ESRD)
and other adverse outcomes
1 NKF Fact Sheets httpwwwkidneyorgnewsnewsroomfactsheetsFastFacts Accessed Nov 5 20142 USRDS wwwusrdsorg Accessed Nov 5 20143 Coresh et al JAMA 2007 2982038-2047
26 million Americans have CKD
Coresh et al 2015
Persistent albu-minuria with
eGFR ge 60
(CKD Stage I-II)
eGFR of 30-59 (CKD
Stage III)
eGFR of 15-29
(CKD Stage IV)
0
5
10
15
20
25
101
155
07
Mill
ions
of
peop
le
26 million American affectedPrevalence is 11-13 of adult population in the US
Data Source Special analyses Medicare 5 percent sample Known CKD stages presented as bars curve showing ldquoAll codesrdquo includes known CKD stages (codes 5851-5855) and the CKD-stage unspecified codes (5859 and remaining
non-585 CKD codes) Note In previous years this graph reported 5859 codes as a component of the stacked bars Abbreviation CKD chronic kidney disease
Trends in prevalence of recognized CKD overall
and by CKD stage among Medicare patients
aged 65+ 2000-2013
Stage I Stage II Stage III Stage IV Stage V
Chronic Kidney Disease (CKD)
USRDS ADR 2007
Prevalence of ESRD has been rising steadily
Prevalence of CKD by stage among NHANES
participants 1988-2012
Data Source National Health and Nutrition Examination Survey (NHANES) 1988ndash1994 1999-2004 amp 2007ndash2012 participants aged 20 amp older Whisker lines indicate 95 confidence intervals Abbreviations CKD chronic kidney disease
Incident ESRD patients rates adjusted for age amp gender
Incidence varies widely by race and ethnicity
Rate
per
mill
ion
popu
lati
on
Af Am
N AmHispanicAsian
WhiteNon-Hispanic
USRDS ADR 2007
Disproportionately affects African Americans and Hispanics
ESRD end stage renal disease USRDS ADR 2007
Diabetes and hypertension are leading causes of CKD
Incident ESRD rates by primary diagnosis adjusted for age gender amp race
USRDSIncident counts amp adjusted rates by age
USRDS ADR 2007
Prevalence of Abnormalities at each level of GFR
0102030405060708090
15-29 30-59 60-89 90+
Estimated GFR (mlmin173 m2)
Pro
porti
on o
f pop
ulat
ion
()
Hypertension Hemoglobin lt 120 gdLUnable to walk 14 mile Serum albumin lt 35 gdLSerum calcium lt 85 mgdL Serum phosphorus gt 45 mgdL
gt14090 or antihypertensive medication p-trend lt 0001 for each abnormality
Prevalence of CKD by age amp risk factor among
NHANES participants 1988-2012
Vol 1 CKD Ch 1 16
Data Source National Health and Nutrition Examination Survey (NHANES) 1988ndash1994 1999-2004 amp 2007ndash2012 participants aged 20 amp older Diabetes defined as either HbA1c gt7 self-reported or currently taking glucose-lowering medications Hypertension defined as BP ge130ge80 for those with diabetes or CKD otherwise BP ge140ge90 or taking medication for hypertension Abbreviations BMI body mass index CKD chronic kidney disease CVD cardiovascular disease DM diabetes mellitus HbA1c glycosylated hemoglobin HTN hypertension SR self-reported
CKD is disproportionately costly
Distribution of costs for CKD HTN amp diabetic patients in Medicare population 20014
Overall expenditures for CKD in the Medicare population age 65 amp older
Point prevalent Medicare CKD patients age 65 amp older costs are total expenditures per calendar year28 of Medicare budget in 2013 up from 69 in 1993
($42 billion in 2013)
USRDS ADR 2013
Data Source Special analyses Medicare 5 percent sample Abbreviations CKD chronic kidney disease CHF congestive heart failure DM diabetes mellitus PPPY per person per year
Per person per year expenditures on Parts A B and D
services for the CKD Medicare population aged 65+ by
DM CHF and year 1993-2013
Per person per month (PPPM) expenditures during the transition to ESRD by dataset 2011
Incident Medicare (age 67 amp older) amp Truven Health MarketScan (younger than 65) ESRD patients initiating in 2008
USRDS ADR 2013
Preventing progression of CKD will help hold
down costs as the treatment of ESRD is expensive requires
some type of replacement therapy
to maintain life
Relationships between cardiac events and loss of life expectancy resulting from CVD by stage of CKD
Marcello Tonelli et al Circulation 2016133518-536The Lancet Gansevoort et al 2013 Elsevier
Data source Special analyses Medicare 5 percent sample January 1 of each reported year point prevalent Medicare patients age 66 and older Ref 2012 patients Abbreviation CKD chronic kidney disease
All-cause mortality rates (per 1000 patient years at
risk) for Medicare patients aged 66+ by CKD status
and year 2001-2013
Data source Special analyses Medicare 5 percent sample January 1 2013 point prevalent patients aged 66 and older Adj agesexrace Ref all patients 2013 Abbreviations CKD chronic kidney disease CVD
cardiovascular disease DM diabetes mellitus
Adjusted all-cause mortality rates (per 1000 patient years at risk) for Medicare patients aged 66+ by cardiovascular disease and diabetes mellitus CKD status and stage 2013
Cardiovascular Mortality in the General Population and in ESRD Treated by Dialysis
001
100
10
1
01
Annual mortality ()
25ndash34 45ndash54 65ndash74 8535ndash44 55ndash64 75ndash84
MaleFemaleBlackWhite
Dialysis
General population
Age (years)
Am J Kidney Dis 2012 39(S2) S1-246
Data Source National Health and Nutrition Examination Survey (NHANES) 2001-2012 participants aged 20 amp older Abbreviations CKD chronic kidney disease
NHANES participants with CKD aware of their
kidney disease 2001-2012
Gaps in CKD Diagnosis In Diabetic Patients
Szczech Lynda A et al Primary Care Detection of Chronic Kidney Disease in Adults with Type-2 Diabetes The ADD-CKD Study (Awareness Detection and Drug Therapy in Type-2 Diabetes and Chronic Kidney Disease) PLOS One - In press (2014)
0204060
CKD Screening in Primary Care( of patients)
of Patients
Improved Diagnosis of CKDIn Diabetic Patients
Studies demonstrate that clinician behavior changes when CKD diagnosis improves Significant improvements realized in1-3
bull Increased urinary albumin testing
bull Increased appropriate use of ACEi or ARBs
bull Avoidance of NSAIDs prescribing among patients with low proteinuria ampor eGFR
bull Appropriate nephrology consultation
1 Wei L et al Kidney Int 201384174-1782 Chan M et al Am J Med 20071201063-10703 Fink J et al Am J Kidney Dis 200953681-668
Plan
What is the Pathophysiology of CKD
Pathophysiology of CKD
Risk Factors and Causes for CKD
Pathophysiology of CKD
Stage I amp II CKDDiminished Renal Reserve
eGFR 50
eGFR
Proteinuria
Glomerulosclerosis
ImpairedSluggish Blood Flow
Modifiable Factors-DM-Hypertension-Increase Protein amp Fat intake-Smoking-Use of NSAIDS
Non-Modifiable Factors-Heriditary-Age greater than 60 yrs old-Gender-Race
Thickening ampor an in the amount of collagen in the
basement membranes of the small vessels
Pathophysiology of CKD
Pathophysiological Events Underlying the Origin and Evolution of Hypertensive Nephropathy
Pathogenesis of kidney disease in patients with diabetes
Muskiet M H A et al (2013) Nat Rev Nephrol doi101038nrneph2013272
Pathophysiology of CKD
Pathophysiology of CKD
Pathogenesis of disordered mineral metabolism in CKD
Increase FGF-23
Hypocalcemia
Increase PTH
Bone Disease
Severe inhibition of 1-α hydroxylase and
125 dihydroxyvitamin D
Vit D DeficiencyVit D Resistance
Hyperphosphatemia
Decrease GFR
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
middot It is progressive tissue destruction with permanent loss of nephrons and renal function
middot CKD stage V eGFR lt 15 mlmin173 m2
middot ESRD is a defined term that indicates advanced CKD which necessitates treatment by Renal Replacement Therapy-RRT (dialysis ampor kidney transplantation)
What is the definition of CKD
CKD as a Public Health Issue
middot Increases risk for all-cause mortality
CV mortality
End stage renal disease (ESRD)
and other adverse outcomes
1 NKF Fact Sheets httpwwwkidneyorgnewsnewsroomfactsheetsFastFacts Accessed Nov 5 20142 USRDS wwwusrdsorg Accessed Nov 5 20143 Coresh et al JAMA 2007 2982038-2047
26 million Americans have CKD
Coresh et al 2015
Persistent albu-minuria with
eGFR ge 60
(CKD Stage I-II)
eGFR of 30-59 (CKD
Stage III)
eGFR of 15-29
(CKD Stage IV)
0
5
10
15
20
25
101
155
07
Mill
ions
of
peop
le
26 million American affectedPrevalence is 11-13 of adult population in the US
Data Source Special analyses Medicare 5 percent sample Known CKD stages presented as bars curve showing ldquoAll codesrdquo includes known CKD stages (codes 5851-5855) and the CKD-stage unspecified codes (5859 and remaining
non-585 CKD codes) Note In previous years this graph reported 5859 codes as a component of the stacked bars Abbreviation CKD chronic kidney disease
Trends in prevalence of recognized CKD overall
and by CKD stage among Medicare patients
aged 65+ 2000-2013
Stage I Stage II Stage III Stage IV Stage V
Chronic Kidney Disease (CKD)
USRDS ADR 2007
Prevalence of ESRD has been rising steadily
Prevalence of CKD by stage among NHANES
participants 1988-2012
Data Source National Health and Nutrition Examination Survey (NHANES) 1988ndash1994 1999-2004 amp 2007ndash2012 participants aged 20 amp older Whisker lines indicate 95 confidence intervals Abbreviations CKD chronic kidney disease
Incident ESRD patients rates adjusted for age amp gender
Incidence varies widely by race and ethnicity
Rate
per
mill
ion
popu
lati
on
Af Am
N AmHispanicAsian
WhiteNon-Hispanic
USRDS ADR 2007
Disproportionately affects African Americans and Hispanics
ESRD end stage renal disease USRDS ADR 2007
Diabetes and hypertension are leading causes of CKD
Incident ESRD rates by primary diagnosis adjusted for age gender amp race
USRDSIncident counts amp adjusted rates by age
USRDS ADR 2007
Prevalence of Abnormalities at each level of GFR
0102030405060708090
15-29 30-59 60-89 90+
Estimated GFR (mlmin173 m2)
Pro
porti
on o
f pop
ulat
ion
()
Hypertension Hemoglobin lt 120 gdLUnable to walk 14 mile Serum albumin lt 35 gdLSerum calcium lt 85 mgdL Serum phosphorus gt 45 mgdL
gt14090 or antihypertensive medication p-trend lt 0001 for each abnormality
Prevalence of CKD by age amp risk factor among
NHANES participants 1988-2012
Vol 1 CKD Ch 1 16
Data Source National Health and Nutrition Examination Survey (NHANES) 1988ndash1994 1999-2004 amp 2007ndash2012 participants aged 20 amp older Diabetes defined as either HbA1c gt7 self-reported or currently taking glucose-lowering medications Hypertension defined as BP ge130ge80 for those with diabetes or CKD otherwise BP ge140ge90 or taking medication for hypertension Abbreviations BMI body mass index CKD chronic kidney disease CVD cardiovascular disease DM diabetes mellitus HbA1c glycosylated hemoglobin HTN hypertension SR self-reported
CKD is disproportionately costly
Distribution of costs for CKD HTN amp diabetic patients in Medicare population 20014
Overall expenditures for CKD in the Medicare population age 65 amp older
Point prevalent Medicare CKD patients age 65 amp older costs are total expenditures per calendar year28 of Medicare budget in 2013 up from 69 in 1993
($42 billion in 2013)
USRDS ADR 2013
Data Source Special analyses Medicare 5 percent sample Abbreviations CKD chronic kidney disease CHF congestive heart failure DM diabetes mellitus PPPY per person per year
Per person per year expenditures on Parts A B and D
services for the CKD Medicare population aged 65+ by
DM CHF and year 1993-2013
Per person per month (PPPM) expenditures during the transition to ESRD by dataset 2011
Incident Medicare (age 67 amp older) amp Truven Health MarketScan (younger than 65) ESRD patients initiating in 2008
USRDS ADR 2013
Preventing progression of CKD will help hold
down costs as the treatment of ESRD is expensive requires
some type of replacement therapy
to maintain life
Relationships between cardiac events and loss of life expectancy resulting from CVD by stage of CKD
Marcello Tonelli et al Circulation 2016133518-536The Lancet Gansevoort et al 2013 Elsevier
Data source Special analyses Medicare 5 percent sample January 1 of each reported year point prevalent Medicare patients age 66 and older Ref 2012 patients Abbreviation CKD chronic kidney disease
All-cause mortality rates (per 1000 patient years at
risk) for Medicare patients aged 66+ by CKD status
and year 2001-2013
Data source Special analyses Medicare 5 percent sample January 1 2013 point prevalent patients aged 66 and older Adj agesexrace Ref all patients 2013 Abbreviations CKD chronic kidney disease CVD
cardiovascular disease DM diabetes mellitus
Adjusted all-cause mortality rates (per 1000 patient years at risk) for Medicare patients aged 66+ by cardiovascular disease and diabetes mellitus CKD status and stage 2013
Cardiovascular Mortality in the General Population and in ESRD Treated by Dialysis
001
100
10
1
01
Annual mortality ()
25ndash34 45ndash54 65ndash74 8535ndash44 55ndash64 75ndash84
MaleFemaleBlackWhite
Dialysis
General population
Age (years)
Am J Kidney Dis 2012 39(S2) S1-246
Data Source National Health and Nutrition Examination Survey (NHANES) 2001-2012 participants aged 20 amp older Abbreviations CKD chronic kidney disease
NHANES participants with CKD aware of their
kidney disease 2001-2012
Gaps in CKD Diagnosis In Diabetic Patients
Szczech Lynda A et al Primary Care Detection of Chronic Kidney Disease in Adults with Type-2 Diabetes The ADD-CKD Study (Awareness Detection and Drug Therapy in Type-2 Diabetes and Chronic Kidney Disease) PLOS One - In press (2014)
0204060
CKD Screening in Primary Care( of patients)
of Patients
Improved Diagnosis of CKDIn Diabetic Patients
Studies demonstrate that clinician behavior changes when CKD diagnosis improves Significant improvements realized in1-3
bull Increased urinary albumin testing
bull Increased appropriate use of ACEi or ARBs
bull Avoidance of NSAIDs prescribing among patients with low proteinuria ampor eGFR
bull Appropriate nephrology consultation
1 Wei L et al Kidney Int 201384174-1782 Chan M et al Am J Med 20071201063-10703 Fink J et al Am J Kidney Dis 200953681-668
Plan
What is the Pathophysiology of CKD
Pathophysiology of CKD
Risk Factors and Causes for CKD
Pathophysiology of CKD
Stage I amp II CKDDiminished Renal Reserve
eGFR 50
eGFR
Proteinuria
Glomerulosclerosis
ImpairedSluggish Blood Flow
Modifiable Factors-DM-Hypertension-Increase Protein amp Fat intake-Smoking-Use of NSAIDS
Non-Modifiable Factors-Heriditary-Age greater than 60 yrs old-Gender-Race
Thickening ampor an in the amount of collagen in the
basement membranes of the small vessels
Pathophysiology of CKD
Pathophysiological Events Underlying the Origin and Evolution of Hypertensive Nephropathy
Pathogenesis of kidney disease in patients with diabetes
Muskiet M H A et al (2013) Nat Rev Nephrol doi101038nrneph2013272
Pathophysiology of CKD
Pathophysiology of CKD
Pathogenesis of disordered mineral metabolism in CKD
Increase FGF-23
Hypocalcemia
Increase PTH
Bone Disease
Severe inhibition of 1-α hydroxylase and
125 dihydroxyvitamin D
Vit D DeficiencyVit D Resistance
Hyperphosphatemia
Decrease GFR
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
CKD as a Public Health Issue
middot Increases risk for all-cause mortality
CV mortality
End stage renal disease (ESRD)
and other adverse outcomes
1 NKF Fact Sheets httpwwwkidneyorgnewsnewsroomfactsheetsFastFacts Accessed Nov 5 20142 USRDS wwwusrdsorg Accessed Nov 5 20143 Coresh et al JAMA 2007 2982038-2047
26 million Americans have CKD
Coresh et al 2015
Persistent albu-minuria with
eGFR ge 60
(CKD Stage I-II)
eGFR of 30-59 (CKD
Stage III)
eGFR of 15-29
(CKD Stage IV)
0
5
10
15
20
25
101
155
07
Mill
ions
of
peop
le
26 million American affectedPrevalence is 11-13 of adult population in the US
Data Source Special analyses Medicare 5 percent sample Known CKD stages presented as bars curve showing ldquoAll codesrdquo includes known CKD stages (codes 5851-5855) and the CKD-stage unspecified codes (5859 and remaining
non-585 CKD codes) Note In previous years this graph reported 5859 codes as a component of the stacked bars Abbreviation CKD chronic kidney disease
Trends in prevalence of recognized CKD overall
and by CKD stage among Medicare patients
aged 65+ 2000-2013
Stage I Stage II Stage III Stage IV Stage V
Chronic Kidney Disease (CKD)
USRDS ADR 2007
Prevalence of ESRD has been rising steadily
Prevalence of CKD by stage among NHANES
participants 1988-2012
Data Source National Health and Nutrition Examination Survey (NHANES) 1988ndash1994 1999-2004 amp 2007ndash2012 participants aged 20 amp older Whisker lines indicate 95 confidence intervals Abbreviations CKD chronic kidney disease
Incident ESRD patients rates adjusted for age amp gender
Incidence varies widely by race and ethnicity
Rate
per
mill
ion
popu
lati
on
Af Am
N AmHispanicAsian
WhiteNon-Hispanic
USRDS ADR 2007
Disproportionately affects African Americans and Hispanics
ESRD end stage renal disease USRDS ADR 2007
Diabetes and hypertension are leading causes of CKD
Incident ESRD rates by primary diagnosis adjusted for age gender amp race
USRDSIncident counts amp adjusted rates by age
USRDS ADR 2007
Prevalence of Abnormalities at each level of GFR
0102030405060708090
15-29 30-59 60-89 90+
Estimated GFR (mlmin173 m2)
Pro
porti
on o
f pop
ulat
ion
()
Hypertension Hemoglobin lt 120 gdLUnable to walk 14 mile Serum albumin lt 35 gdLSerum calcium lt 85 mgdL Serum phosphorus gt 45 mgdL
gt14090 or antihypertensive medication p-trend lt 0001 for each abnormality
Prevalence of CKD by age amp risk factor among
NHANES participants 1988-2012
Vol 1 CKD Ch 1 16
Data Source National Health and Nutrition Examination Survey (NHANES) 1988ndash1994 1999-2004 amp 2007ndash2012 participants aged 20 amp older Diabetes defined as either HbA1c gt7 self-reported or currently taking glucose-lowering medications Hypertension defined as BP ge130ge80 for those with diabetes or CKD otherwise BP ge140ge90 or taking medication for hypertension Abbreviations BMI body mass index CKD chronic kidney disease CVD cardiovascular disease DM diabetes mellitus HbA1c glycosylated hemoglobin HTN hypertension SR self-reported
CKD is disproportionately costly
Distribution of costs for CKD HTN amp diabetic patients in Medicare population 20014
Overall expenditures for CKD in the Medicare population age 65 amp older
Point prevalent Medicare CKD patients age 65 amp older costs are total expenditures per calendar year28 of Medicare budget in 2013 up from 69 in 1993
($42 billion in 2013)
USRDS ADR 2013
Data Source Special analyses Medicare 5 percent sample Abbreviations CKD chronic kidney disease CHF congestive heart failure DM diabetes mellitus PPPY per person per year
Per person per year expenditures on Parts A B and D
services for the CKD Medicare population aged 65+ by
DM CHF and year 1993-2013
Per person per month (PPPM) expenditures during the transition to ESRD by dataset 2011
Incident Medicare (age 67 amp older) amp Truven Health MarketScan (younger than 65) ESRD patients initiating in 2008
USRDS ADR 2013
Preventing progression of CKD will help hold
down costs as the treatment of ESRD is expensive requires
some type of replacement therapy
to maintain life
Relationships between cardiac events and loss of life expectancy resulting from CVD by stage of CKD
Marcello Tonelli et al Circulation 2016133518-536The Lancet Gansevoort et al 2013 Elsevier
Data source Special analyses Medicare 5 percent sample January 1 of each reported year point prevalent Medicare patients age 66 and older Ref 2012 patients Abbreviation CKD chronic kidney disease
All-cause mortality rates (per 1000 patient years at
risk) for Medicare patients aged 66+ by CKD status
and year 2001-2013
Data source Special analyses Medicare 5 percent sample January 1 2013 point prevalent patients aged 66 and older Adj agesexrace Ref all patients 2013 Abbreviations CKD chronic kidney disease CVD
cardiovascular disease DM diabetes mellitus
Adjusted all-cause mortality rates (per 1000 patient years at risk) for Medicare patients aged 66+ by cardiovascular disease and diabetes mellitus CKD status and stage 2013
Cardiovascular Mortality in the General Population and in ESRD Treated by Dialysis
001
100
10
1
01
Annual mortality ()
25ndash34 45ndash54 65ndash74 8535ndash44 55ndash64 75ndash84
MaleFemaleBlackWhite
Dialysis
General population
Age (years)
Am J Kidney Dis 2012 39(S2) S1-246
Data Source National Health and Nutrition Examination Survey (NHANES) 2001-2012 participants aged 20 amp older Abbreviations CKD chronic kidney disease
NHANES participants with CKD aware of their
kidney disease 2001-2012
Gaps in CKD Diagnosis In Diabetic Patients
Szczech Lynda A et al Primary Care Detection of Chronic Kidney Disease in Adults with Type-2 Diabetes The ADD-CKD Study (Awareness Detection and Drug Therapy in Type-2 Diabetes and Chronic Kidney Disease) PLOS One - In press (2014)
0204060
CKD Screening in Primary Care( of patients)
of Patients
Improved Diagnosis of CKDIn Diabetic Patients
Studies demonstrate that clinician behavior changes when CKD diagnosis improves Significant improvements realized in1-3
bull Increased urinary albumin testing
bull Increased appropriate use of ACEi or ARBs
bull Avoidance of NSAIDs prescribing among patients with low proteinuria ampor eGFR
bull Appropriate nephrology consultation
1 Wei L et al Kidney Int 201384174-1782 Chan M et al Am J Med 20071201063-10703 Fink J et al Am J Kidney Dis 200953681-668
Plan
What is the Pathophysiology of CKD
Pathophysiology of CKD
Risk Factors and Causes for CKD
Pathophysiology of CKD
Stage I amp II CKDDiminished Renal Reserve
eGFR 50
eGFR
Proteinuria
Glomerulosclerosis
ImpairedSluggish Blood Flow
Modifiable Factors-DM-Hypertension-Increase Protein amp Fat intake-Smoking-Use of NSAIDS
Non-Modifiable Factors-Heriditary-Age greater than 60 yrs old-Gender-Race
Thickening ampor an in the amount of collagen in the
basement membranes of the small vessels
Pathophysiology of CKD
Pathophysiological Events Underlying the Origin and Evolution of Hypertensive Nephropathy
Pathogenesis of kidney disease in patients with diabetes
Muskiet M H A et al (2013) Nat Rev Nephrol doi101038nrneph2013272
Pathophysiology of CKD
Pathophysiology of CKD
Pathogenesis of disordered mineral metabolism in CKD
Increase FGF-23
Hypocalcemia
Increase PTH
Bone Disease
Severe inhibition of 1-α hydroxylase and
125 dihydroxyvitamin D
Vit D DeficiencyVit D Resistance
Hyperphosphatemia
Decrease GFR
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
26 million Americans have CKD
Coresh et al 2015
Persistent albu-minuria with
eGFR ge 60
(CKD Stage I-II)
eGFR of 30-59 (CKD
Stage III)
eGFR of 15-29
(CKD Stage IV)
0
5
10
15
20
25
101
155
07
Mill
ions
of
peop
le
26 million American affectedPrevalence is 11-13 of adult population in the US
Data Source Special analyses Medicare 5 percent sample Known CKD stages presented as bars curve showing ldquoAll codesrdquo includes known CKD stages (codes 5851-5855) and the CKD-stage unspecified codes (5859 and remaining
non-585 CKD codes) Note In previous years this graph reported 5859 codes as a component of the stacked bars Abbreviation CKD chronic kidney disease
Trends in prevalence of recognized CKD overall
and by CKD stage among Medicare patients
aged 65+ 2000-2013
Stage I Stage II Stage III Stage IV Stage V
Chronic Kidney Disease (CKD)
USRDS ADR 2007
Prevalence of ESRD has been rising steadily
Prevalence of CKD by stage among NHANES
participants 1988-2012
Data Source National Health and Nutrition Examination Survey (NHANES) 1988ndash1994 1999-2004 amp 2007ndash2012 participants aged 20 amp older Whisker lines indicate 95 confidence intervals Abbreviations CKD chronic kidney disease
Incident ESRD patients rates adjusted for age amp gender
Incidence varies widely by race and ethnicity
Rate
per
mill
ion
popu
lati
on
Af Am
N AmHispanicAsian
WhiteNon-Hispanic
USRDS ADR 2007
Disproportionately affects African Americans and Hispanics
ESRD end stage renal disease USRDS ADR 2007
Diabetes and hypertension are leading causes of CKD
Incident ESRD rates by primary diagnosis adjusted for age gender amp race
USRDSIncident counts amp adjusted rates by age
USRDS ADR 2007
Prevalence of Abnormalities at each level of GFR
0102030405060708090
15-29 30-59 60-89 90+
Estimated GFR (mlmin173 m2)
Pro
porti
on o
f pop
ulat
ion
()
Hypertension Hemoglobin lt 120 gdLUnable to walk 14 mile Serum albumin lt 35 gdLSerum calcium lt 85 mgdL Serum phosphorus gt 45 mgdL
gt14090 or antihypertensive medication p-trend lt 0001 for each abnormality
Prevalence of CKD by age amp risk factor among
NHANES participants 1988-2012
Vol 1 CKD Ch 1 16
Data Source National Health and Nutrition Examination Survey (NHANES) 1988ndash1994 1999-2004 amp 2007ndash2012 participants aged 20 amp older Diabetes defined as either HbA1c gt7 self-reported or currently taking glucose-lowering medications Hypertension defined as BP ge130ge80 for those with diabetes or CKD otherwise BP ge140ge90 or taking medication for hypertension Abbreviations BMI body mass index CKD chronic kidney disease CVD cardiovascular disease DM diabetes mellitus HbA1c glycosylated hemoglobin HTN hypertension SR self-reported
CKD is disproportionately costly
Distribution of costs for CKD HTN amp diabetic patients in Medicare population 20014
Overall expenditures for CKD in the Medicare population age 65 amp older
Point prevalent Medicare CKD patients age 65 amp older costs are total expenditures per calendar year28 of Medicare budget in 2013 up from 69 in 1993
($42 billion in 2013)
USRDS ADR 2013
Data Source Special analyses Medicare 5 percent sample Abbreviations CKD chronic kidney disease CHF congestive heart failure DM diabetes mellitus PPPY per person per year
Per person per year expenditures on Parts A B and D
services for the CKD Medicare population aged 65+ by
DM CHF and year 1993-2013
Per person per month (PPPM) expenditures during the transition to ESRD by dataset 2011
Incident Medicare (age 67 amp older) amp Truven Health MarketScan (younger than 65) ESRD patients initiating in 2008
USRDS ADR 2013
Preventing progression of CKD will help hold
down costs as the treatment of ESRD is expensive requires
some type of replacement therapy
to maintain life
Relationships between cardiac events and loss of life expectancy resulting from CVD by stage of CKD
Marcello Tonelli et al Circulation 2016133518-536The Lancet Gansevoort et al 2013 Elsevier
Data source Special analyses Medicare 5 percent sample January 1 of each reported year point prevalent Medicare patients age 66 and older Ref 2012 patients Abbreviation CKD chronic kidney disease
All-cause mortality rates (per 1000 patient years at
risk) for Medicare patients aged 66+ by CKD status
and year 2001-2013
Data source Special analyses Medicare 5 percent sample January 1 2013 point prevalent patients aged 66 and older Adj agesexrace Ref all patients 2013 Abbreviations CKD chronic kidney disease CVD
cardiovascular disease DM diabetes mellitus
Adjusted all-cause mortality rates (per 1000 patient years at risk) for Medicare patients aged 66+ by cardiovascular disease and diabetes mellitus CKD status and stage 2013
Cardiovascular Mortality in the General Population and in ESRD Treated by Dialysis
001
100
10
1
01
Annual mortality ()
25ndash34 45ndash54 65ndash74 8535ndash44 55ndash64 75ndash84
MaleFemaleBlackWhite
Dialysis
General population
Age (years)
Am J Kidney Dis 2012 39(S2) S1-246
Data Source National Health and Nutrition Examination Survey (NHANES) 2001-2012 participants aged 20 amp older Abbreviations CKD chronic kidney disease
NHANES participants with CKD aware of their
kidney disease 2001-2012
Gaps in CKD Diagnosis In Diabetic Patients
Szczech Lynda A et al Primary Care Detection of Chronic Kidney Disease in Adults with Type-2 Diabetes The ADD-CKD Study (Awareness Detection and Drug Therapy in Type-2 Diabetes and Chronic Kidney Disease) PLOS One - In press (2014)
0204060
CKD Screening in Primary Care( of patients)
of Patients
Improved Diagnosis of CKDIn Diabetic Patients
Studies demonstrate that clinician behavior changes when CKD diagnosis improves Significant improvements realized in1-3
bull Increased urinary albumin testing
bull Increased appropriate use of ACEi or ARBs
bull Avoidance of NSAIDs prescribing among patients with low proteinuria ampor eGFR
bull Appropriate nephrology consultation
1 Wei L et al Kidney Int 201384174-1782 Chan M et al Am J Med 20071201063-10703 Fink J et al Am J Kidney Dis 200953681-668
Plan
What is the Pathophysiology of CKD
Pathophysiology of CKD
Risk Factors and Causes for CKD
Pathophysiology of CKD
Stage I amp II CKDDiminished Renal Reserve
eGFR 50
eGFR
Proteinuria
Glomerulosclerosis
ImpairedSluggish Blood Flow
Modifiable Factors-DM-Hypertension-Increase Protein amp Fat intake-Smoking-Use of NSAIDS
Non-Modifiable Factors-Heriditary-Age greater than 60 yrs old-Gender-Race
Thickening ampor an in the amount of collagen in the
basement membranes of the small vessels
Pathophysiology of CKD
Pathophysiological Events Underlying the Origin and Evolution of Hypertensive Nephropathy
Pathogenesis of kidney disease in patients with diabetes
Muskiet M H A et al (2013) Nat Rev Nephrol doi101038nrneph2013272
Pathophysiology of CKD
Pathophysiology of CKD
Pathogenesis of disordered mineral metabolism in CKD
Increase FGF-23
Hypocalcemia
Increase PTH
Bone Disease
Severe inhibition of 1-α hydroxylase and
125 dihydroxyvitamin D
Vit D DeficiencyVit D Resistance
Hyperphosphatemia
Decrease GFR
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Data Source Special analyses Medicare 5 percent sample Known CKD stages presented as bars curve showing ldquoAll codesrdquo includes known CKD stages (codes 5851-5855) and the CKD-stage unspecified codes (5859 and remaining
non-585 CKD codes) Note In previous years this graph reported 5859 codes as a component of the stacked bars Abbreviation CKD chronic kidney disease
Trends in prevalence of recognized CKD overall
and by CKD stage among Medicare patients
aged 65+ 2000-2013
Stage I Stage II Stage III Stage IV Stage V
Chronic Kidney Disease (CKD)
USRDS ADR 2007
Prevalence of ESRD has been rising steadily
Prevalence of CKD by stage among NHANES
participants 1988-2012
Data Source National Health and Nutrition Examination Survey (NHANES) 1988ndash1994 1999-2004 amp 2007ndash2012 participants aged 20 amp older Whisker lines indicate 95 confidence intervals Abbreviations CKD chronic kidney disease
Incident ESRD patients rates adjusted for age amp gender
Incidence varies widely by race and ethnicity
Rate
per
mill
ion
popu
lati
on
Af Am
N AmHispanicAsian
WhiteNon-Hispanic
USRDS ADR 2007
Disproportionately affects African Americans and Hispanics
ESRD end stage renal disease USRDS ADR 2007
Diabetes and hypertension are leading causes of CKD
Incident ESRD rates by primary diagnosis adjusted for age gender amp race
USRDSIncident counts amp adjusted rates by age
USRDS ADR 2007
Prevalence of Abnormalities at each level of GFR
0102030405060708090
15-29 30-59 60-89 90+
Estimated GFR (mlmin173 m2)
Pro
porti
on o
f pop
ulat
ion
()
Hypertension Hemoglobin lt 120 gdLUnable to walk 14 mile Serum albumin lt 35 gdLSerum calcium lt 85 mgdL Serum phosphorus gt 45 mgdL
gt14090 or antihypertensive medication p-trend lt 0001 for each abnormality
Prevalence of CKD by age amp risk factor among
NHANES participants 1988-2012
Vol 1 CKD Ch 1 16
Data Source National Health and Nutrition Examination Survey (NHANES) 1988ndash1994 1999-2004 amp 2007ndash2012 participants aged 20 amp older Diabetes defined as either HbA1c gt7 self-reported or currently taking glucose-lowering medications Hypertension defined as BP ge130ge80 for those with diabetes or CKD otherwise BP ge140ge90 or taking medication for hypertension Abbreviations BMI body mass index CKD chronic kidney disease CVD cardiovascular disease DM diabetes mellitus HbA1c glycosylated hemoglobin HTN hypertension SR self-reported
CKD is disproportionately costly
Distribution of costs for CKD HTN amp diabetic patients in Medicare population 20014
Overall expenditures for CKD in the Medicare population age 65 amp older
Point prevalent Medicare CKD patients age 65 amp older costs are total expenditures per calendar year28 of Medicare budget in 2013 up from 69 in 1993
($42 billion in 2013)
USRDS ADR 2013
Data Source Special analyses Medicare 5 percent sample Abbreviations CKD chronic kidney disease CHF congestive heart failure DM diabetes mellitus PPPY per person per year
Per person per year expenditures on Parts A B and D
services for the CKD Medicare population aged 65+ by
DM CHF and year 1993-2013
Per person per month (PPPM) expenditures during the transition to ESRD by dataset 2011
Incident Medicare (age 67 amp older) amp Truven Health MarketScan (younger than 65) ESRD patients initiating in 2008
USRDS ADR 2013
Preventing progression of CKD will help hold
down costs as the treatment of ESRD is expensive requires
some type of replacement therapy
to maintain life
Relationships between cardiac events and loss of life expectancy resulting from CVD by stage of CKD
Marcello Tonelli et al Circulation 2016133518-536The Lancet Gansevoort et al 2013 Elsevier
Data source Special analyses Medicare 5 percent sample January 1 of each reported year point prevalent Medicare patients age 66 and older Ref 2012 patients Abbreviation CKD chronic kidney disease
All-cause mortality rates (per 1000 patient years at
risk) for Medicare patients aged 66+ by CKD status
and year 2001-2013
Data source Special analyses Medicare 5 percent sample January 1 2013 point prevalent patients aged 66 and older Adj agesexrace Ref all patients 2013 Abbreviations CKD chronic kidney disease CVD
cardiovascular disease DM diabetes mellitus
Adjusted all-cause mortality rates (per 1000 patient years at risk) for Medicare patients aged 66+ by cardiovascular disease and diabetes mellitus CKD status and stage 2013
Cardiovascular Mortality in the General Population and in ESRD Treated by Dialysis
001
100
10
1
01
Annual mortality ()
25ndash34 45ndash54 65ndash74 8535ndash44 55ndash64 75ndash84
MaleFemaleBlackWhite
Dialysis
General population
Age (years)
Am J Kidney Dis 2012 39(S2) S1-246
Data Source National Health and Nutrition Examination Survey (NHANES) 2001-2012 participants aged 20 amp older Abbreviations CKD chronic kidney disease
NHANES participants with CKD aware of their
kidney disease 2001-2012
Gaps in CKD Diagnosis In Diabetic Patients
Szczech Lynda A et al Primary Care Detection of Chronic Kidney Disease in Adults with Type-2 Diabetes The ADD-CKD Study (Awareness Detection and Drug Therapy in Type-2 Diabetes and Chronic Kidney Disease) PLOS One - In press (2014)
0204060
CKD Screening in Primary Care( of patients)
of Patients
Improved Diagnosis of CKDIn Diabetic Patients
Studies demonstrate that clinician behavior changes when CKD diagnosis improves Significant improvements realized in1-3
bull Increased urinary albumin testing
bull Increased appropriate use of ACEi or ARBs
bull Avoidance of NSAIDs prescribing among patients with low proteinuria ampor eGFR
bull Appropriate nephrology consultation
1 Wei L et al Kidney Int 201384174-1782 Chan M et al Am J Med 20071201063-10703 Fink J et al Am J Kidney Dis 200953681-668
Plan
What is the Pathophysiology of CKD
Pathophysiology of CKD
Risk Factors and Causes for CKD
Pathophysiology of CKD
Stage I amp II CKDDiminished Renal Reserve
eGFR 50
eGFR
Proteinuria
Glomerulosclerosis
ImpairedSluggish Blood Flow
Modifiable Factors-DM-Hypertension-Increase Protein amp Fat intake-Smoking-Use of NSAIDS
Non-Modifiable Factors-Heriditary-Age greater than 60 yrs old-Gender-Race
Thickening ampor an in the amount of collagen in the
basement membranes of the small vessels
Pathophysiology of CKD
Pathophysiological Events Underlying the Origin and Evolution of Hypertensive Nephropathy
Pathogenesis of kidney disease in patients with diabetes
Muskiet M H A et al (2013) Nat Rev Nephrol doi101038nrneph2013272
Pathophysiology of CKD
Pathophysiology of CKD
Pathogenesis of disordered mineral metabolism in CKD
Increase FGF-23
Hypocalcemia
Increase PTH
Bone Disease
Severe inhibition of 1-α hydroxylase and
125 dihydroxyvitamin D
Vit D DeficiencyVit D Resistance
Hyperphosphatemia
Decrease GFR
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
USRDS ADR 2007
Prevalence of ESRD has been rising steadily
Prevalence of CKD by stage among NHANES
participants 1988-2012
Data Source National Health and Nutrition Examination Survey (NHANES) 1988ndash1994 1999-2004 amp 2007ndash2012 participants aged 20 amp older Whisker lines indicate 95 confidence intervals Abbreviations CKD chronic kidney disease
Incident ESRD patients rates adjusted for age amp gender
Incidence varies widely by race and ethnicity
Rate
per
mill
ion
popu
lati
on
Af Am
N AmHispanicAsian
WhiteNon-Hispanic
USRDS ADR 2007
Disproportionately affects African Americans and Hispanics
ESRD end stage renal disease USRDS ADR 2007
Diabetes and hypertension are leading causes of CKD
Incident ESRD rates by primary diagnosis adjusted for age gender amp race
USRDSIncident counts amp adjusted rates by age
USRDS ADR 2007
Prevalence of Abnormalities at each level of GFR
0102030405060708090
15-29 30-59 60-89 90+
Estimated GFR (mlmin173 m2)
Pro
porti
on o
f pop
ulat
ion
()
Hypertension Hemoglobin lt 120 gdLUnable to walk 14 mile Serum albumin lt 35 gdLSerum calcium lt 85 mgdL Serum phosphorus gt 45 mgdL
gt14090 or antihypertensive medication p-trend lt 0001 for each abnormality
Prevalence of CKD by age amp risk factor among
NHANES participants 1988-2012
Vol 1 CKD Ch 1 16
Data Source National Health and Nutrition Examination Survey (NHANES) 1988ndash1994 1999-2004 amp 2007ndash2012 participants aged 20 amp older Diabetes defined as either HbA1c gt7 self-reported or currently taking glucose-lowering medications Hypertension defined as BP ge130ge80 for those with diabetes or CKD otherwise BP ge140ge90 or taking medication for hypertension Abbreviations BMI body mass index CKD chronic kidney disease CVD cardiovascular disease DM diabetes mellitus HbA1c glycosylated hemoglobin HTN hypertension SR self-reported
CKD is disproportionately costly
Distribution of costs for CKD HTN amp diabetic patients in Medicare population 20014
Overall expenditures for CKD in the Medicare population age 65 amp older
Point prevalent Medicare CKD patients age 65 amp older costs are total expenditures per calendar year28 of Medicare budget in 2013 up from 69 in 1993
($42 billion in 2013)
USRDS ADR 2013
Data Source Special analyses Medicare 5 percent sample Abbreviations CKD chronic kidney disease CHF congestive heart failure DM diabetes mellitus PPPY per person per year
Per person per year expenditures on Parts A B and D
services for the CKD Medicare population aged 65+ by
DM CHF and year 1993-2013
Per person per month (PPPM) expenditures during the transition to ESRD by dataset 2011
Incident Medicare (age 67 amp older) amp Truven Health MarketScan (younger than 65) ESRD patients initiating in 2008
USRDS ADR 2013
Preventing progression of CKD will help hold
down costs as the treatment of ESRD is expensive requires
some type of replacement therapy
to maintain life
Relationships between cardiac events and loss of life expectancy resulting from CVD by stage of CKD
Marcello Tonelli et al Circulation 2016133518-536The Lancet Gansevoort et al 2013 Elsevier
Data source Special analyses Medicare 5 percent sample January 1 of each reported year point prevalent Medicare patients age 66 and older Ref 2012 patients Abbreviation CKD chronic kidney disease
All-cause mortality rates (per 1000 patient years at
risk) for Medicare patients aged 66+ by CKD status
and year 2001-2013
Data source Special analyses Medicare 5 percent sample January 1 2013 point prevalent patients aged 66 and older Adj agesexrace Ref all patients 2013 Abbreviations CKD chronic kidney disease CVD
cardiovascular disease DM diabetes mellitus
Adjusted all-cause mortality rates (per 1000 patient years at risk) for Medicare patients aged 66+ by cardiovascular disease and diabetes mellitus CKD status and stage 2013
Cardiovascular Mortality in the General Population and in ESRD Treated by Dialysis
001
100
10
1
01
Annual mortality ()
25ndash34 45ndash54 65ndash74 8535ndash44 55ndash64 75ndash84
MaleFemaleBlackWhite
Dialysis
General population
Age (years)
Am J Kidney Dis 2012 39(S2) S1-246
Data Source National Health and Nutrition Examination Survey (NHANES) 2001-2012 participants aged 20 amp older Abbreviations CKD chronic kidney disease
NHANES participants with CKD aware of their
kidney disease 2001-2012
Gaps in CKD Diagnosis In Diabetic Patients
Szczech Lynda A et al Primary Care Detection of Chronic Kidney Disease in Adults with Type-2 Diabetes The ADD-CKD Study (Awareness Detection and Drug Therapy in Type-2 Diabetes and Chronic Kidney Disease) PLOS One - In press (2014)
0204060
CKD Screening in Primary Care( of patients)
of Patients
Improved Diagnosis of CKDIn Diabetic Patients
Studies demonstrate that clinician behavior changes when CKD diagnosis improves Significant improvements realized in1-3
bull Increased urinary albumin testing
bull Increased appropriate use of ACEi or ARBs
bull Avoidance of NSAIDs prescribing among patients with low proteinuria ampor eGFR
bull Appropriate nephrology consultation
1 Wei L et al Kidney Int 201384174-1782 Chan M et al Am J Med 20071201063-10703 Fink J et al Am J Kidney Dis 200953681-668
Plan
What is the Pathophysiology of CKD
Pathophysiology of CKD
Risk Factors and Causes for CKD
Pathophysiology of CKD
Stage I amp II CKDDiminished Renal Reserve
eGFR 50
eGFR
Proteinuria
Glomerulosclerosis
ImpairedSluggish Blood Flow
Modifiable Factors-DM-Hypertension-Increase Protein amp Fat intake-Smoking-Use of NSAIDS
Non-Modifiable Factors-Heriditary-Age greater than 60 yrs old-Gender-Race
Thickening ampor an in the amount of collagen in the
basement membranes of the small vessels
Pathophysiology of CKD
Pathophysiological Events Underlying the Origin and Evolution of Hypertensive Nephropathy
Pathogenesis of kidney disease in patients with diabetes
Muskiet M H A et al (2013) Nat Rev Nephrol doi101038nrneph2013272
Pathophysiology of CKD
Pathophysiology of CKD
Pathogenesis of disordered mineral metabolism in CKD
Increase FGF-23
Hypocalcemia
Increase PTH
Bone Disease
Severe inhibition of 1-α hydroxylase and
125 dihydroxyvitamin D
Vit D DeficiencyVit D Resistance
Hyperphosphatemia
Decrease GFR
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Prevalence of CKD by stage among NHANES
participants 1988-2012
Data Source National Health and Nutrition Examination Survey (NHANES) 1988ndash1994 1999-2004 amp 2007ndash2012 participants aged 20 amp older Whisker lines indicate 95 confidence intervals Abbreviations CKD chronic kidney disease
Incident ESRD patients rates adjusted for age amp gender
Incidence varies widely by race and ethnicity
Rate
per
mill
ion
popu
lati
on
Af Am
N AmHispanicAsian
WhiteNon-Hispanic
USRDS ADR 2007
Disproportionately affects African Americans and Hispanics
ESRD end stage renal disease USRDS ADR 2007
Diabetes and hypertension are leading causes of CKD
Incident ESRD rates by primary diagnosis adjusted for age gender amp race
USRDSIncident counts amp adjusted rates by age
USRDS ADR 2007
Prevalence of Abnormalities at each level of GFR
0102030405060708090
15-29 30-59 60-89 90+
Estimated GFR (mlmin173 m2)
Pro
porti
on o
f pop
ulat
ion
()
Hypertension Hemoglobin lt 120 gdLUnable to walk 14 mile Serum albumin lt 35 gdLSerum calcium lt 85 mgdL Serum phosphorus gt 45 mgdL
gt14090 or antihypertensive medication p-trend lt 0001 for each abnormality
Prevalence of CKD by age amp risk factor among
NHANES participants 1988-2012
Vol 1 CKD Ch 1 16
Data Source National Health and Nutrition Examination Survey (NHANES) 1988ndash1994 1999-2004 amp 2007ndash2012 participants aged 20 amp older Diabetes defined as either HbA1c gt7 self-reported or currently taking glucose-lowering medications Hypertension defined as BP ge130ge80 for those with diabetes or CKD otherwise BP ge140ge90 or taking medication for hypertension Abbreviations BMI body mass index CKD chronic kidney disease CVD cardiovascular disease DM diabetes mellitus HbA1c glycosylated hemoglobin HTN hypertension SR self-reported
CKD is disproportionately costly
Distribution of costs for CKD HTN amp diabetic patients in Medicare population 20014
Overall expenditures for CKD in the Medicare population age 65 amp older
Point prevalent Medicare CKD patients age 65 amp older costs are total expenditures per calendar year28 of Medicare budget in 2013 up from 69 in 1993
($42 billion in 2013)
USRDS ADR 2013
Data Source Special analyses Medicare 5 percent sample Abbreviations CKD chronic kidney disease CHF congestive heart failure DM diabetes mellitus PPPY per person per year
Per person per year expenditures on Parts A B and D
services for the CKD Medicare population aged 65+ by
DM CHF and year 1993-2013
Per person per month (PPPM) expenditures during the transition to ESRD by dataset 2011
Incident Medicare (age 67 amp older) amp Truven Health MarketScan (younger than 65) ESRD patients initiating in 2008
USRDS ADR 2013
Preventing progression of CKD will help hold
down costs as the treatment of ESRD is expensive requires
some type of replacement therapy
to maintain life
Relationships between cardiac events and loss of life expectancy resulting from CVD by stage of CKD
Marcello Tonelli et al Circulation 2016133518-536The Lancet Gansevoort et al 2013 Elsevier
Data source Special analyses Medicare 5 percent sample January 1 of each reported year point prevalent Medicare patients age 66 and older Ref 2012 patients Abbreviation CKD chronic kidney disease
All-cause mortality rates (per 1000 patient years at
risk) for Medicare patients aged 66+ by CKD status
and year 2001-2013
Data source Special analyses Medicare 5 percent sample January 1 2013 point prevalent patients aged 66 and older Adj agesexrace Ref all patients 2013 Abbreviations CKD chronic kidney disease CVD
cardiovascular disease DM diabetes mellitus
Adjusted all-cause mortality rates (per 1000 patient years at risk) for Medicare patients aged 66+ by cardiovascular disease and diabetes mellitus CKD status and stage 2013
Cardiovascular Mortality in the General Population and in ESRD Treated by Dialysis
001
100
10
1
01
Annual mortality ()
25ndash34 45ndash54 65ndash74 8535ndash44 55ndash64 75ndash84
MaleFemaleBlackWhite
Dialysis
General population
Age (years)
Am J Kidney Dis 2012 39(S2) S1-246
Data Source National Health and Nutrition Examination Survey (NHANES) 2001-2012 participants aged 20 amp older Abbreviations CKD chronic kidney disease
NHANES participants with CKD aware of their
kidney disease 2001-2012
Gaps in CKD Diagnosis In Diabetic Patients
Szczech Lynda A et al Primary Care Detection of Chronic Kidney Disease in Adults with Type-2 Diabetes The ADD-CKD Study (Awareness Detection and Drug Therapy in Type-2 Diabetes and Chronic Kidney Disease) PLOS One - In press (2014)
0204060
CKD Screening in Primary Care( of patients)
of Patients
Improved Diagnosis of CKDIn Diabetic Patients
Studies demonstrate that clinician behavior changes when CKD diagnosis improves Significant improvements realized in1-3
bull Increased urinary albumin testing
bull Increased appropriate use of ACEi or ARBs
bull Avoidance of NSAIDs prescribing among patients with low proteinuria ampor eGFR
bull Appropriate nephrology consultation
1 Wei L et al Kidney Int 201384174-1782 Chan M et al Am J Med 20071201063-10703 Fink J et al Am J Kidney Dis 200953681-668
Plan
What is the Pathophysiology of CKD
Pathophysiology of CKD
Risk Factors and Causes for CKD
Pathophysiology of CKD
Stage I amp II CKDDiminished Renal Reserve
eGFR 50
eGFR
Proteinuria
Glomerulosclerosis
ImpairedSluggish Blood Flow
Modifiable Factors-DM-Hypertension-Increase Protein amp Fat intake-Smoking-Use of NSAIDS
Non-Modifiable Factors-Heriditary-Age greater than 60 yrs old-Gender-Race
Thickening ampor an in the amount of collagen in the
basement membranes of the small vessels
Pathophysiology of CKD
Pathophysiological Events Underlying the Origin and Evolution of Hypertensive Nephropathy
Pathogenesis of kidney disease in patients with diabetes
Muskiet M H A et al (2013) Nat Rev Nephrol doi101038nrneph2013272
Pathophysiology of CKD
Pathophysiology of CKD
Pathogenesis of disordered mineral metabolism in CKD
Increase FGF-23
Hypocalcemia
Increase PTH
Bone Disease
Severe inhibition of 1-α hydroxylase and
125 dihydroxyvitamin D
Vit D DeficiencyVit D Resistance
Hyperphosphatemia
Decrease GFR
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Incident ESRD patients rates adjusted for age amp gender
Incidence varies widely by race and ethnicity
Rate
per
mill
ion
popu
lati
on
Af Am
N AmHispanicAsian
WhiteNon-Hispanic
USRDS ADR 2007
Disproportionately affects African Americans and Hispanics
ESRD end stage renal disease USRDS ADR 2007
Diabetes and hypertension are leading causes of CKD
Incident ESRD rates by primary diagnosis adjusted for age gender amp race
USRDSIncident counts amp adjusted rates by age
USRDS ADR 2007
Prevalence of Abnormalities at each level of GFR
0102030405060708090
15-29 30-59 60-89 90+
Estimated GFR (mlmin173 m2)
Pro
porti
on o
f pop
ulat
ion
()
Hypertension Hemoglobin lt 120 gdLUnable to walk 14 mile Serum albumin lt 35 gdLSerum calcium lt 85 mgdL Serum phosphorus gt 45 mgdL
gt14090 or antihypertensive medication p-trend lt 0001 for each abnormality
Prevalence of CKD by age amp risk factor among
NHANES participants 1988-2012
Vol 1 CKD Ch 1 16
Data Source National Health and Nutrition Examination Survey (NHANES) 1988ndash1994 1999-2004 amp 2007ndash2012 participants aged 20 amp older Diabetes defined as either HbA1c gt7 self-reported or currently taking glucose-lowering medications Hypertension defined as BP ge130ge80 for those with diabetes or CKD otherwise BP ge140ge90 or taking medication for hypertension Abbreviations BMI body mass index CKD chronic kidney disease CVD cardiovascular disease DM diabetes mellitus HbA1c glycosylated hemoglobin HTN hypertension SR self-reported
CKD is disproportionately costly
Distribution of costs for CKD HTN amp diabetic patients in Medicare population 20014
Overall expenditures for CKD in the Medicare population age 65 amp older
Point prevalent Medicare CKD patients age 65 amp older costs are total expenditures per calendar year28 of Medicare budget in 2013 up from 69 in 1993
($42 billion in 2013)
USRDS ADR 2013
Data Source Special analyses Medicare 5 percent sample Abbreviations CKD chronic kidney disease CHF congestive heart failure DM diabetes mellitus PPPY per person per year
Per person per year expenditures on Parts A B and D
services for the CKD Medicare population aged 65+ by
DM CHF and year 1993-2013
Per person per month (PPPM) expenditures during the transition to ESRD by dataset 2011
Incident Medicare (age 67 amp older) amp Truven Health MarketScan (younger than 65) ESRD patients initiating in 2008
USRDS ADR 2013
Preventing progression of CKD will help hold
down costs as the treatment of ESRD is expensive requires
some type of replacement therapy
to maintain life
Relationships between cardiac events and loss of life expectancy resulting from CVD by stage of CKD
Marcello Tonelli et al Circulation 2016133518-536The Lancet Gansevoort et al 2013 Elsevier
Data source Special analyses Medicare 5 percent sample January 1 of each reported year point prevalent Medicare patients age 66 and older Ref 2012 patients Abbreviation CKD chronic kidney disease
All-cause mortality rates (per 1000 patient years at
risk) for Medicare patients aged 66+ by CKD status
and year 2001-2013
Data source Special analyses Medicare 5 percent sample January 1 2013 point prevalent patients aged 66 and older Adj agesexrace Ref all patients 2013 Abbreviations CKD chronic kidney disease CVD
cardiovascular disease DM diabetes mellitus
Adjusted all-cause mortality rates (per 1000 patient years at risk) for Medicare patients aged 66+ by cardiovascular disease and diabetes mellitus CKD status and stage 2013
Cardiovascular Mortality in the General Population and in ESRD Treated by Dialysis
001
100
10
1
01
Annual mortality ()
25ndash34 45ndash54 65ndash74 8535ndash44 55ndash64 75ndash84
MaleFemaleBlackWhite
Dialysis
General population
Age (years)
Am J Kidney Dis 2012 39(S2) S1-246
Data Source National Health and Nutrition Examination Survey (NHANES) 2001-2012 participants aged 20 amp older Abbreviations CKD chronic kidney disease
NHANES participants with CKD aware of their
kidney disease 2001-2012
Gaps in CKD Diagnosis In Diabetic Patients
Szczech Lynda A et al Primary Care Detection of Chronic Kidney Disease in Adults with Type-2 Diabetes The ADD-CKD Study (Awareness Detection and Drug Therapy in Type-2 Diabetes and Chronic Kidney Disease) PLOS One - In press (2014)
0204060
CKD Screening in Primary Care( of patients)
of Patients
Improved Diagnosis of CKDIn Diabetic Patients
Studies demonstrate that clinician behavior changes when CKD diagnosis improves Significant improvements realized in1-3
bull Increased urinary albumin testing
bull Increased appropriate use of ACEi or ARBs
bull Avoidance of NSAIDs prescribing among patients with low proteinuria ampor eGFR
bull Appropriate nephrology consultation
1 Wei L et al Kidney Int 201384174-1782 Chan M et al Am J Med 20071201063-10703 Fink J et al Am J Kidney Dis 200953681-668
Plan
What is the Pathophysiology of CKD
Pathophysiology of CKD
Risk Factors and Causes for CKD
Pathophysiology of CKD
Stage I amp II CKDDiminished Renal Reserve
eGFR 50
eGFR
Proteinuria
Glomerulosclerosis
ImpairedSluggish Blood Flow
Modifiable Factors-DM-Hypertension-Increase Protein amp Fat intake-Smoking-Use of NSAIDS
Non-Modifiable Factors-Heriditary-Age greater than 60 yrs old-Gender-Race
Thickening ampor an in the amount of collagen in the
basement membranes of the small vessels
Pathophysiology of CKD
Pathophysiological Events Underlying the Origin and Evolution of Hypertensive Nephropathy
Pathogenesis of kidney disease in patients with diabetes
Muskiet M H A et al (2013) Nat Rev Nephrol doi101038nrneph2013272
Pathophysiology of CKD
Pathophysiology of CKD
Pathogenesis of disordered mineral metabolism in CKD
Increase FGF-23
Hypocalcemia
Increase PTH
Bone Disease
Severe inhibition of 1-α hydroxylase and
125 dihydroxyvitamin D
Vit D DeficiencyVit D Resistance
Hyperphosphatemia
Decrease GFR
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
ESRD end stage renal disease USRDS ADR 2007
Diabetes and hypertension are leading causes of CKD
Incident ESRD rates by primary diagnosis adjusted for age gender amp race
USRDSIncident counts amp adjusted rates by age
USRDS ADR 2007
Prevalence of Abnormalities at each level of GFR
0102030405060708090
15-29 30-59 60-89 90+
Estimated GFR (mlmin173 m2)
Pro
porti
on o
f pop
ulat
ion
()
Hypertension Hemoglobin lt 120 gdLUnable to walk 14 mile Serum albumin lt 35 gdLSerum calcium lt 85 mgdL Serum phosphorus gt 45 mgdL
gt14090 or antihypertensive medication p-trend lt 0001 for each abnormality
Prevalence of CKD by age amp risk factor among
NHANES participants 1988-2012
Vol 1 CKD Ch 1 16
Data Source National Health and Nutrition Examination Survey (NHANES) 1988ndash1994 1999-2004 amp 2007ndash2012 participants aged 20 amp older Diabetes defined as either HbA1c gt7 self-reported or currently taking glucose-lowering medications Hypertension defined as BP ge130ge80 for those with diabetes or CKD otherwise BP ge140ge90 or taking medication for hypertension Abbreviations BMI body mass index CKD chronic kidney disease CVD cardiovascular disease DM diabetes mellitus HbA1c glycosylated hemoglobin HTN hypertension SR self-reported
CKD is disproportionately costly
Distribution of costs for CKD HTN amp diabetic patients in Medicare population 20014
Overall expenditures for CKD in the Medicare population age 65 amp older
Point prevalent Medicare CKD patients age 65 amp older costs are total expenditures per calendar year28 of Medicare budget in 2013 up from 69 in 1993
($42 billion in 2013)
USRDS ADR 2013
Data Source Special analyses Medicare 5 percent sample Abbreviations CKD chronic kidney disease CHF congestive heart failure DM diabetes mellitus PPPY per person per year
Per person per year expenditures on Parts A B and D
services for the CKD Medicare population aged 65+ by
DM CHF and year 1993-2013
Per person per month (PPPM) expenditures during the transition to ESRD by dataset 2011
Incident Medicare (age 67 amp older) amp Truven Health MarketScan (younger than 65) ESRD patients initiating in 2008
USRDS ADR 2013
Preventing progression of CKD will help hold
down costs as the treatment of ESRD is expensive requires
some type of replacement therapy
to maintain life
Relationships between cardiac events and loss of life expectancy resulting from CVD by stage of CKD
Marcello Tonelli et al Circulation 2016133518-536The Lancet Gansevoort et al 2013 Elsevier
Data source Special analyses Medicare 5 percent sample January 1 of each reported year point prevalent Medicare patients age 66 and older Ref 2012 patients Abbreviation CKD chronic kidney disease
All-cause mortality rates (per 1000 patient years at
risk) for Medicare patients aged 66+ by CKD status
and year 2001-2013
Data source Special analyses Medicare 5 percent sample January 1 2013 point prevalent patients aged 66 and older Adj agesexrace Ref all patients 2013 Abbreviations CKD chronic kidney disease CVD
cardiovascular disease DM diabetes mellitus
Adjusted all-cause mortality rates (per 1000 patient years at risk) for Medicare patients aged 66+ by cardiovascular disease and diabetes mellitus CKD status and stage 2013
Cardiovascular Mortality in the General Population and in ESRD Treated by Dialysis
001
100
10
1
01
Annual mortality ()
25ndash34 45ndash54 65ndash74 8535ndash44 55ndash64 75ndash84
MaleFemaleBlackWhite
Dialysis
General population
Age (years)
Am J Kidney Dis 2012 39(S2) S1-246
Data Source National Health and Nutrition Examination Survey (NHANES) 2001-2012 participants aged 20 amp older Abbreviations CKD chronic kidney disease
NHANES participants with CKD aware of their
kidney disease 2001-2012
Gaps in CKD Diagnosis In Diabetic Patients
Szczech Lynda A et al Primary Care Detection of Chronic Kidney Disease in Adults with Type-2 Diabetes The ADD-CKD Study (Awareness Detection and Drug Therapy in Type-2 Diabetes and Chronic Kidney Disease) PLOS One - In press (2014)
0204060
CKD Screening in Primary Care( of patients)
of Patients
Improved Diagnosis of CKDIn Diabetic Patients
Studies demonstrate that clinician behavior changes when CKD diagnosis improves Significant improvements realized in1-3
bull Increased urinary albumin testing
bull Increased appropriate use of ACEi or ARBs
bull Avoidance of NSAIDs prescribing among patients with low proteinuria ampor eGFR
bull Appropriate nephrology consultation
1 Wei L et al Kidney Int 201384174-1782 Chan M et al Am J Med 20071201063-10703 Fink J et al Am J Kidney Dis 200953681-668
Plan
What is the Pathophysiology of CKD
Pathophysiology of CKD
Risk Factors and Causes for CKD
Pathophysiology of CKD
Stage I amp II CKDDiminished Renal Reserve
eGFR 50
eGFR
Proteinuria
Glomerulosclerosis
ImpairedSluggish Blood Flow
Modifiable Factors-DM-Hypertension-Increase Protein amp Fat intake-Smoking-Use of NSAIDS
Non-Modifiable Factors-Heriditary-Age greater than 60 yrs old-Gender-Race
Thickening ampor an in the amount of collagen in the
basement membranes of the small vessels
Pathophysiology of CKD
Pathophysiological Events Underlying the Origin and Evolution of Hypertensive Nephropathy
Pathogenesis of kidney disease in patients with diabetes
Muskiet M H A et al (2013) Nat Rev Nephrol doi101038nrneph2013272
Pathophysiology of CKD
Pathophysiology of CKD
Pathogenesis of disordered mineral metabolism in CKD
Increase FGF-23
Hypocalcemia
Increase PTH
Bone Disease
Severe inhibition of 1-α hydroxylase and
125 dihydroxyvitamin D
Vit D DeficiencyVit D Resistance
Hyperphosphatemia
Decrease GFR
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
USRDSIncident counts amp adjusted rates by age
USRDS ADR 2007
Prevalence of Abnormalities at each level of GFR
0102030405060708090
15-29 30-59 60-89 90+
Estimated GFR (mlmin173 m2)
Pro
porti
on o
f pop
ulat
ion
()
Hypertension Hemoglobin lt 120 gdLUnable to walk 14 mile Serum albumin lt 35 gdLSerum calcium lt 85 mgdL Serum phosphorus gt 45 mgdL
gt14090 or antihypertensive medication p-trend lt 0001 for each abnormality
Prevalence of CKD by age amp risk factor among
NHANES participants 1988-2012
Vol 1 CKD Ch 1 16
Data Source National Health and Nutrition Examination Survey (NHANES) 1988ndash1994 1999-2004 amp 2007ndash2012 participants aged 20 amp older Diabetes defined as either HbA1c gt7 self-reported or currently taking glucose-lowering medications Hypertension defined as BP ge130ge80 for those with diabetes or CKD otherwise BP ge140ge90 or taking medication for hypertension Abbreviations BMI body mass index CKD chronic kidney disease CVD cardiovascular disease DM diabetes mellitus HbA1c glycosylated hemoglobin HTN hypertension SR self-reported
CKD is disproportionately costly
Distribution of costs for CKD HTN amp diabetic patients in Medicare population 20014
Overall expenditures for CKD in the Medicare population age 65 amp older
Point prevalent Medicare CKD patients age 65 amp older costs are total expenditures per calendar year28 of Medicare budget in 2013 up from 69 in 1993
($42 billion in 2013)
USRDS ADR 2013
Data Source Special analyses Medicare 5 percent sample Abbreviations CKD chronic kidney disease CHF congestive heart failure DM diabetes mellitus PPPY per person per year
Per person per year expenditures on Parts A B and D
services for the CKD Medicare population aged 65+ by
DM CHF and year 1993-2013
Per person per month (PPPM) expenditures during the transition to ESRD by dataset 2011
Incident Medicare (age 67 amp older) amp Truven Health MarketScan (younger than 65) ESRD patients initiating in 2008
USRDS ADR 2013
Preventing progression of CKD will help hold
down costs as the treatment of ESRD is expensive requires
some type of replacement therapy
to maintain life
Relationships between cardiac events and loss of life expectancy resulting from CVD by stage of CKD
Marcello Tonelli et al Circulation 2016133518-536The Lancet Gansevoort et al 2013 Elsevier
Data source Special analyses Medicare 5 percent sample January 1 of each reported year point prevalent Medicare patients age 66 and older Ref 2012 patients Abbreviation CKD chronic kidney disease
All-cause mortality rates (per 1000 patient years at
risk) for Medicare patients aged 66+ by CKD status
and year 2001-2013
Data source Special analyses Medicare 5 percent sample January 1 2013 point prevalent patients aged 66 and older Adj agesexrace Ref all patients 2013 Abbreviations CKD chronic kidney disease CVD
cardiovascular disease DM diabetes mellitus
Adjusted all-cause mortality rates (per 1000 patient years at risk) for Medicare patients aged 66+ by cardiovascular disease and diabetes mellitus CKD status and stage 2013
Cardiovascular Mortality in the General Population and in ESRD Treated by Dialysis
001
100
10
1
01
Annual mortality ()
25ndash34 45ndash54 65ndash74 8535ndash44 55ndash64 75ndash84
MaleFemaleBlackWhite
Dialysis
General population
Age (years)
Am J Kidney Dis 2012 39(S2) S1-246
Data Source National Health and Nutrition Examination Survey (NHANES) 2001-2012 participants aged 20 amp older Abbreviations CKD chronic kidney disease
NHANES participants with CKD aware of their
kidney disease 2001-2012
Gaps in CKD Diagnosis In Diabetic Patients
Szczech Lynda A et al Primary Care Detection of Chronic Kidney Disease in Adults with Type-2 Diabetes The ADD-CKD Study (Awareness Detection and Drug Therapy in Type-2 Diabetes and Chronic Kidney Disease) PLOS One - In press (2014)
0204060
CKD Screening in Primary Care( of patients)
of Patients
Improved Diagnosis of CKDIn Diabetic Patients
Studies demonstrate that clinician behavior changes when CKD diagnosis improves Significant improvements realized in1-3
bull Increased urinary albumin testing
bull Increased appropriate use of ACEi or ARBs
bull Avoidance of NSAIDs prescribing among patients with low proteinuria ampor eGFR
bull Appropriate nephrology consultation
1 Wei L et al Kidney Int 201384174-1782 Chan M et al Am J Med 20071201063-10703 Fink J et al Am J Kidney Dis 200953681-668
Plan
What is the Pathophysiology of CKD
Pathophysiology of CKD
Risk Factors and Causes for CKD
Pathophysiology of CKD
Stage I amp II CKDDiminished Renal Reserve
eGFR 50
eGFR
Proteinuria
Glomerulosclerosis
ImpairedSluggish Blood Flow
Modifiable Factors-DM-Hypertension-Increase Protein amp Fat intake-Smoking-Use of NSAIDS
Non-Modifiable Factors-Heriditary-Age greater than 60 yrs old-Gender-Race
Thickening ampor an in the amount of collagen in the
basement membranes of the small vessels
Pathophysiology of CKD
Pathophysiological Events Underlying the Origin and Evolution of Hypertensive Nephropathy
Pathogenesis of kidney disease in patients with diabetes
Muskiet M H A et al (2013) Nat Rev Nephrol doi101038nrneph2013272
Pathophysiology of CKD
Pathophysiology of CKD
Pathogenesis of disordered mineral metabolism in CKD
Increase FGF-23
Hypocalcemia
Increase PTH
Bone Disease
Severe inhibition of 1-α hydroxylase and
125 dihydroxyvitamin D
Vit D DeficiencyVit D Resistance
Hyperphosphatemia
Decrease GFR
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Prevalence of Abnormalities at each level of GFR
0102030405060708090
15-29 30-59 60-89 90+
Estimated GFR (mlmin173 m2)
Pro
porti
on o
f pop
ulat
ion
()
Hypertension Hemoglobin lt 120 gdLUnable to walk 14 mile Serum albumin lt 35 gdLSerum calcium lt 85 mgdL Serum phosphorus gt 45 mgdL
gt14090 or antihypertensive medication p-trend lt 0001 for each abnormality
Prevalence of CKD by age amp risk factor among
NHANES participants 1988-2012
Vol 1 CKD Ch 1 16
Data Source National Health and Nutrition Examination Survey (NHANES) 1988ndash1994 1999-2004 amp 2007ndash2012 participants aged 20 amp older Diabetes defined as either HbA1c gt7 self-reported or currently taking glucose-lowering medications Hypertension defined as BP ge130ge80 for those with diabetes or CKD otherwise BP ge140ge90 or taking medication for hypertension Abbreviations BMI body mass index CKD chronic kidney disease CVD cardiovascular disease DM diabetes mellitus HbA1c glycosylated hemoglobin HTN hypertension SR self-reported
CKD is disproportionately costly
Distribution of costs for CKD HTN amp diabetic patients in Medicare population 20014
Overall expenditures for CKD in the Medicare population age 65 amp older
Point prevalent Medicare CKD patients age 65 amp older costs are total expenditures per calendar year28 of Medicare budget in 2013 up from 69 in 1993
($42 billion in 2013)
USRDS ADR 2013
Data Source Special analyses Medicare 5 percent sample Abbreviations CKD chronic kidney disease CHF congestive heart failure DM diabetes mellitus PPPY per person per year
Per person per year expenditures on Parts A B and D
services for the CKD Medicare population aged 65+ by
DM CHF and year 1993-2013
Per person per month (PPPM) expenditures during the transition to ESRD by dataset 2011
Incident Medicare (age 67 amp older) amp Truven Health MarketScan (younger than 65) ESRD patients initiating in 2008
USRDS ADR 2013
Preventing progression of CKD will help hold
down costs as the treatment of ESRD is expensive requires
some type of replacement therapy
to maintain life
Relationships between cardiac events and loss of life expectancy resulting from CVD by stage of CKD
Marcello Tonelli et al Circulation 2016133518-536The Lancet Gansevoort et al 2013 Elsevier
Data source Special analyses Medicare 5 percent sample January 1 of each reported year point prevalent Medicare patients age 66 and older Ref 2012 patients Abbreviation CKD chronic kidney disease
All-cause mortality rates (per 1000 patient years at
risk) for Medicare patients aged 66+ by CKD status
and year 2001-2013
Data source Special analyses Medicare 5 percent sample January 1 2013 point prevalent patients aged 66 and older Adj agesexrace Ref all patients 2013 Abbreviations CKD chronic kidney disease CVD
cardiovascular disease DM diabetes mellitus
Adjusted all-cause mortality rates (per 1000 patient years at risk) for Medicare patients aged 66+ by cardiovascular disease and diabetes mellitus CKD status and stage 2013
Cardiovascular Mortality in the General Population and in ESRD Treated by Dialysis
001
100
10
1
01
Annual mortality ()
25ndash34 45ndash54 65ndash74 8535ndash44 55ndash64 75ndash84
MaleFemaleBlackWhite
Dialysis
General population
Age (years)
Am J Kidney Dis 2012 39(S2) S1-246
Data Source National Health and Nutrition Examination Survey (NHANES) 2001-2012 participants aged 20 amp older Abbreviations CKD chronic kidney disease
NHANES participants with CKD aware of their
kidney disease 2001-2012
Gaps in CKD Diagnosis In Diabetic Patients
Szczech Lynda A et al Primary Care Detection of Chronic Kidney Disease in Adults with Type-2 Diabetes The ADD-CKD Study (Awareness Detection and Drug Therapy in Type-2 Diabetes and Chronic Kidney Disease) PLOS One - In press (2014)
0204060
CKD Screening in Primary Care( of patients)
of Patients
Improved Diagnosis of CKDIn Diabetic Patients
Studies demonstrate that clinician behavior changes when CKD diagnosis improves Significant improvements realized in1-3
bull Increased urinary albumin testing
bull Increased appropriate use of ACEi or ARBs
bull Avoidance of NSAIDs prescribing among patients with low proteinuria ampor eGFR
bull Appropriate nephrology consultation
1 Wei L et al Kidney Int 201384174-1782 Chan M et al Am J Med 20071201063-10703 Fink J et al Am J Kidney Dis 200953681-668
Plan
What is the Pathophysiology of CKD
Pathophysiology of CKD
Risk Factors and Causes for CKD
Pathophysiology of CKD
Stage I amp II CKDDiminished Renal Reserve
eGFR 50
eGFR
Proteinuria
Glomerulosclerosis
ImpairedSluggish Blood Flow
Modifiable Factors-DM-Hypertension-Increase Protein amp Fat intake-Smoking-Use of NSAIDS
Non-Modifiable Factors-Heriditary-Age greater than 60 yrs old-Gender-Race
Thickening ampor an in the amount of collagen in the
basement membranes of the small vessels
Pathophysiology of CKD
Pathophysiological Events Underlying the Origin and Evolution of Hypertensive Nephropathy
Pathogenesis of kidney disease in patients with diabetes
Muskiet M H A et al (2013) Nat Rev Nephrol doi101038nrneph2013272
Pathophysiology of CKD
Pathophysiology of CKD
Pathogenesis of disordered mineral metabolism in CKD
Increase FGF-23
Hypocalcemia
Increase PTH
Bone Disease
Severe inhibition of 1-α hydroxylase and
125 dihydroxyvitamin D
Vit D DeficiencyVit D Resistance
Hyperphosphatemia
Decrease GFR
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Prevalence of CKD by age amp risk factor among
NHANES participants 1988-2012
Vol 1 CKD Ch 1 16
Data Source National Health and Nutrition Examination Survey (NHANES) 1988ndash1994 1999-2004 amp 2007ndash2012 participants aged 20 amp older Diabetes defined as either HbA1c gt7 self-reported or currently taking glucose-lowering medications Hypertension defined as BP ge130ge80 for those with diabetes or CKD otherwise BP ge140ge90 or taking medication for hypertension Abbreviations BMI body mass index CKD chronic kidney disease CVD cardiovascular disease DM diabetes mellitus HbA1c glycosylated hemoglobin HTN hypertension SR self-reported
CKD is disproportionately costly
Distribution of costs for CKD HTN amp diabetic patients in Medicare population 20014
Overall expenditures for CKD in the Medicare population age 65 amp older
Point prevalent Medicare CKD patients age 65 amp older costs are total expenditures per calendar year28 of Medicare budget in 2013 up from 69 in 1993
($42 billion in 2013)
USRDS ADR 2013
Data Source Special analyses Medicare 5 percent sample Abbreviations CKD chronic kidney disease CHF congestive heart failure DM diabetes mellitus PPPY per person per year
Per person per year expenditures on Parts A B and D
services for the CKD Medicare population aged 65+ by
DM CHF and year 1993-2013
Per person per month (PPPM) expenditures during the transition to ESRD by dataset 2011
Incident Medicare (age 67 amp older) amp Truven Health MarketScan (younger than 65) ESRD patients initiating in 2008
USRDS ADR 2013
Preventing progression of CKD will help hold
down costs as the treatment of ESRD is expensive requires
some type of replacement therapy
to maintain life
Relationships between cardiac events and loss of life expectancy resulting from CVD by stage of CKD
Marcello Tonelli et al Circulation 2016133518-536The Lancet Gansevoort et al 2013 Elsevier
Data source Special analyses Medicare 5 percent sample January 1 of each reported year point prevalent Medicare patients age 66 and older Ref 2012 patients Abbreviation CKD chronic kidney disease
All-cause mortality rates (per 1000 patient years at
risk) for Medicare patients aged 66+ by CKD status
and year 2001-2013
Data source Special analyses Medicare 5 percent sample January 1 2013 point prevalent patients aged 66 and older Adj agesexrace Ref all patients 2013 Abbreviations CKD chronic kidney disease CVD
cardiovascular disease DM diabetes mellitus
Adjusted all-cause mortality rates (per 1000 patient years at risk) for Medicare patients aged 66+ by cardiovascular disease and diabetes mellitus CKD status and stage 2013
Cardiovascular Mortality in the General Population and in ESRD Treated by Dialysis
001
100
10
1
01
Annual mortality ()
25ndash34 45ndash54 65ndash74 8535ndash44 55ndash64 75ndash84
MaleFemaleBlackWhite
Dialysis
General population
Age (years)
Am J Kidney Dis 2012 39(S2) S1-246
Data Source National Health and Nutrition Examination Survey (NHANES) 2001-2012 participants aged 20 amp older Abbreviations CKD chronic kidney disease
NHANES participants with CKD aware of their
kidney disease 2001-2012
Gaps in CKD Diagnosis In Diabetic Patients
Szczech Lynda A et al Primary Care Detection of Chronic Kidney Disease in Adults with Type-2 Diabetes The ADD-CKD Study (Awareness Detection and Drug Therapy in Type-2 Diabetes and Chronic Kidney Disease) PLOS One - In press (2014)
0204060
CKD Screening in Primary Care( of patients)
of Patients
Improved Diagnosis of CKDIn Diabetic Patients
Studies demonstrate that clinician behavior changes when CKD diagnosis improves Significant improvements realized in1-3
bull Increased urinary albumin testing
bull Increased appropriate use of ACEi or ARBs
bull Avoidance of NSAIDs prescribing among patients with low proteinuria ampor eGFR
bull Appropriate nephrology consultation
1 Wei L et al Kidney Int 201384174-1782 Chan M et al Am J Med 20071201063-10703 Fink J et al Am J Kidney Dis 200953681-668
Plan
What is the Pathophysiology of CKD
Pathophysiology of CKD
Risk Factors and Causes for CKD
Pathophysiology of CKD
Stage I amp II CKDDiminished Renal Reserve
eGFR 50
eGFR
Proteinuria
Glomerulosclerosis
ImpairedSluggish Blood Flow
Modifiable Factors-DM-Hypertension-Increase Protein amp Fat intake-Smoking-Use of NSAIDS
Non-Modifiable Factors-Heriditary-Age greater than 60 yrs old-Gender-Race
Thickening ampor an in the amount of collagen in the
basement membranes of the small vessels
Pathophysiology of CKD
Pathophysiological Events Underlying the Origin and Evolution of Hypertensive Nephropathy
Pathogenesis of kidney disease in patients with diabetes
Muskiet M H A et al (2013) Nat Rev Nephrol doi101038nrneph2013272
Pathophysiology of CKD
Pathophysiology of CKD
Pathogenesis of disordered mineral metabolism in CKD
Increase FGF-23
Hypocalcemia
Increase PTH
Bone Disease
Severe inhibition of 1-α hydroxylase and
125 dihydroxyvitamin D
Vit D DeficiencyVit D Resistance
Hyperphosphatemia
Decrease GFR
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
CKD is disproportionately costly
Distribution of costs for CKD HTN amp diabetic patients in Medicare population 20014
Overall expenditures for CKD in the Medicare population age 65 amp older
Point prevalent Medicare CKD patients age 65 amp older costs are total expenditures per calendar year28 of Medicare budget in 2013 up from 69 in 1993
($42 billion in 2013)
USRDS ADR 2013
Data Source Special analyses Medicare 5 percent sample Abbreviations CKD chronic kidney disease CHF congestive heart failure DM diabetes mellitus PPPY per person per year
Per person per year expenditures on Parts A B and D
services for the CKD Medicare population aged 65+ by
DM CHF and year 1993-2013
Per person per month (PPPM) expenditures during the transition to ESRD by dataset 2011
Incident Medicare (age 67 amp older) amp Truven Health MarketScan (younger than 65) ESRD patients initiating in 2008
USRDS ADR 2013
Preventing progression of CKD will help hold
down costs as the treatment of ESRD is expensive requires
some type of replacement therapy
to maintain life
Relationships between cardiac events and loss of life expectancy resulting from CVD by stage of CKD
Marcello Tonelli et al Circulation 2016133518-536The Lancet Gansevoort et al 2013 Elsevier
Data source Special analyses Medicare 5 percent sample January 1 of each reported year point prevalent Medicare patients age 66 and older Ref 2012 patients Abbreviation CKD chronic kidney disease
All-cause mortality rates (per 1000 patient years at
risk) for Medicare patients aged 66+ by CKD status
and year 2001-2013
Data source Special analyses Medicare 5 percent sample January 1 2013 point prevalent patients aged 66 and older Adj agesexrace Ref all patients 2013 Abbreviations CKD chronic kidney disease CVD
cardiovascular disease DM diabetes mellitus
Adjusted all-cause mortality rates (per 1000 patient years at risk) for Medicare patients aged 66+ by cardiovascular disease and diabetes mellitus CKD status and stage 2013
Cardiovascular Mortality in the General Population and in ESRD Treated by Dialysis
001
100
10
1
01
Annual mortality ()
25ndash34 45ndash54 65ndash74 8535ndash44 55ndash64 75ndash84
MaleFemaleBlackWhite
Dialysis
General population
Age (years)
Am J Kidney Dis 2012 39(S2) S1-246
Data Source National Health and Nutrition Examination Survey (NHANES) 2001-2012 participants aged 20 amp older Abbreviations CKD chronic kidney disease
NHANES participants with CKD aware of their
kidney disease 2001-2012
Gaps in CKD Diagnosis In Diabetic Patients
Szczech Lynda A et al Primary Care Detection of Chronic Kidney Disease in Adults with Type-2 Diabetes The ADD-CKD Study (Awareness Detection and Drug Therapy in Type-2 Diabetes and Chronic Kidney Disease) PLOS One - In press (2014)
0204060
CKD Screening in Primary Care( of patients)
of Patients
Improved Diagnosis of CKDIn Diabetic Patients
Studies demonstrate that clinician behavior changes when CKD diagnosis improves Significant improvements realized in1-3
bull Increased urinary albumin testing
bull Increased appropriate use of ACEi or ARBs
bull Avoidance of NSAIDs prescribing among patients with low proteinuria ampor eGFR
bull Appropriate nephrology consultation
1 Wei L et al Kidney Int 201384174-1782 Chan M et al Am J Med 20071201063-10703 Fink J et al Am J Kidney Dis 200953681-668
Plan
What is the Pathophysiology of CKD
Pathophysiology of CKD
Risk Factors and Causes for CKD
Pathophysiology of CKD
Stage I amp II CKDDiminished Renal Reserve
eGFR 50
eGFR
Proteinuria
Glomerulosclerosis
ImpairedSluggish Blood Flow
Modifiable Factors-DM-Hypertension-Increase Protein amp Fat intake-Smoking-Use of NSAIDS
Non-Modifiable Factors-Heriditary-Age greater than 60 yrs old-Gender-Race
Thickening ampor an in the amount of collagen in the
basement membranes of the small vessels
Pathophysiology of CKD
Pathophysiological Events Underlying the Origin and Evolution of Hypertensive Nephropathy
Pathogenesis of kidney disease in patients with diabetes
Muskiet M H A et al (2013) Nat Rev Nephrol doi101038nrneph2013272
Pathophysiology of CKD
Pathophysiology of CKD
Pathogenesis of disordered mineral metabolism in CKD
Increase FGF-23
Hypocalcemia
Increase PTH
Bone Disease
Severe inhibition of 1-α hydroxylase and
125 dihydroxyvitamin D
Vit D DeficiencyVit D Resistance
Hyperphosphatemia
Decrease GFR
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Overall expenditures for CKD in the Medicare population age 65 amp older
Point prevalent Medicare CKD patients age 65 amp older costs are total expenditures per calendar year28 of Medicare budget in 2013 up from 69 in 1993
($42 billion in 2013)
USRDS ADR 2013
Data Source Special analyses Medicare 5 percent sample Abbreviations CKD chronic kidney disease CHF congestive heart failure DM diabetes mellitus PPPY per person per year
Per person per year expenditures on Parts A B and D
services for the CKD Medicare population aged 65+ by
DM CHF and year 1993-2013
Per person per month (PPPM) expenditures during the transition to ESRD by dataset 2011
Incident Medicare (age 67 amp older) amp Truven Health MarketScan (younger than 65) ESRD patients initiating in 2008
USRDS ADR 2013
Preventing progression of CKD will help hold
down costs as the treatment of ESRD is expensive requires
some type of replacement therapy
to maintain life
Relationships between cardiac events and loss of life expectancy resulting from CVD by stage of CKD
Marcello Tonelli et al Circulation 2016133518-536The Lancet Gansevoort et al 2013 Elsevier
Data source Special analyses Medicare 5 percent sample January 1 of each reported year point prevalent Medicare patients age 66 and older Ref 2012 patients Abbreviation CKD chronic kidney disease
All-cause mortality rates (per 1000 patient years at
risk) for Medicare patients aged 66+ by CKD status
and year 2001-2013
Data source Special analyses Medicare 5 percent sample January 1 2013 point prevalent patients aged 66 and older Adj agesexrace Ref all patients 2013 Abbreviations CKD chronic kidney disease CVD
cardiovascular disease DM diabetes mellitus
Adjusted all-cause mortality rates (per 1000 patient years at risk) for Medicare patients aged 66+ by cardiovascular disease and diabetes mellitus CKD status and stage 2013
Cardiovascular Mortality in the General Population and in ESRD Treated by Dialysis
001
100
10
1
01
Annual mortality ()
25ndash34 45ndash54 65ndash74 8535ndash44 55ndash64 75ndash84
MaleFemaleBlackWhite
Dialysis
General population
Age (years)
Am J Kidney Dis 2012 39(S2) S1-246
Data Source National Health and Nutrition Examination Survey (NHANES) 2001-2012 participants aged 20 amp older Abbreviations CKD chronic kidney disease
NHANES participants with CKD aware of their
kidney disease 2001-2012
Gaps in CKD Diagnosis In Diabetic Patients
Szczech Lynda A et al Primary Care Detection of Chronic Kidney Disease in Adults with Type-2 Diabetes The ADD-CKD Study (Awareness Detection and Drug Therapy in Type-2 Diabetes and Chronic Kidney Disease) PLOS One - In press (2014)
0204060
CKD Screening in Primary Care( of patients)
of Patients
Improved Diagnosis of CKDIn Diabetic Patients
Studies demonstrate that clinician behavior changes when CKD diagnosis improves Significant improvements realized in1-3
bull Increased urinary albumin testing
bull Increased appropriate use of ACEi or ARBs
bull Avoidance of NSAIDs prescribing among patients with low proteinuria ampor eGFR
bull Appropriate nephrology consultation
1 Wei L et al Kidney Int 201384174-1782 Chan M et al Am J Med 20071201063-10703 Fink J et al Am J Kidney Dis 200953681-668
Plan
What is the Pathophysiology of CKD
Pathophysiology of CKD
Risk Factors and Causes for CKD
Pathophysiology of CKD
Stage I amp II CKDDiminished Renal Reserve
eGFR 50
eGFR
Proteinuria
Glomerulosclerosis
ImpairedSluggish Blood Flow
Modifiable Factors-DM-Hypertension-Increase Protein amp Fat intake-Smoking-Use of NSAIDS
Non-Modifiable Factors-Heriditary-Age greater than 60 yrs old-Gender-Race
Thickening ampor an in the amount of collagen in the
basement membranes of the small vessels
Pathophysiology of CKD
Pathophysiological Events Underlying the Origin and Evolution of Hypertensive Nephropathy
Pathogenesis of kidney disease in patients with diabetes
Muskiet M H A et al (2013) Nat Rev Nephrol doi101038nrneph2013272
Pathophysiology of CKD
Pathophysiology of CKD
Pathogenesis of disordered mineral metabolism in CKD
Increase FGF-23
Hypocalcemia
Increase PTH
Bone Disease
Severe inhibition of 1-α hydroxylase and
125 dihydroxyvitamin D
Vit D DeficiencyVit D Resistance
Hyperphosphatemia
Decrease GFR
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Data Source Special analyses Medicare 5 percent sample Abbreviations CKD chronic kidney disease CHF congestive heart failure DM diabetes mellitus PPPY per person per year
Per person per year expenditures on Parts A B and D
services for the CKD Medicare population aged 65+ by
DM CHF and year 1993-2013
Per person per month (PPPM) expenditures during the transition to ESRD by dataset 2011
Incident Medicare (age 67 amp older) amp Truven Health MarketScan (younger than 65) ESRD patients initiating in 2008
USRDS ADR 2013
Preventing progression of CKD will help hold
down costs as the treatment of ESRD is expensive requires
some type of replacement therapy
to maintain life
Relationships between cardiac events and loss of life expectancy resulting from CVD by stage of CKD
Marcello Tonelli et al Circulation 2016133518-536The Lancet Gansevoort et al 2013 Elsevier
Data source Special analyses Medicare 5 percent sample January 1 of each reported year point prevalent Medicare patients age 66 and older Ref 2012 patients Abbreviation CKD chronic kidney disease
All-cause mortality rates (per 1000 patient years at
risk) for Medicare patients aged 66+ by CKD status
and year 2001-2013
Data source Special analyses Medicare 5 percent sample January 1 2013 point prevalent patients aged 66 and older Adj agesexrace Ref all patients 2013 Abbreviations CKD chronic kidney disease CVD
cardiovascular disease DM diabetes mellitus
Adjusted all-cause mortality rates (per 1000 patient years at risk) for Medicare patients aged 66+ by cardiovascular disease and diabetes mellitus CKD status and stage 2013
Cardiovascular Mortality in the General Population and in ESRD Treated by Dialysis
001
100
10
1
01
Annual mortality ()
25ndash34 45ndash54 65ndash74 8535ndash44 55ndash64 75ndash84
MaleFemaleBlackWhite
Dialysis
General population
Age (years)
Am J Kidney Dis 2012 39(S2) S1-246
Data Source National Health and Nutrition Examination Survey (NHANES) 2001-2012 participants aged 20 amp older Abbreviations CKD chronic kidney disease
NHANES participants with CKD aware of their
kidney disease 2001-2012
Gaps in CKD Diagnosis In Diabetic Patients
Szczech Lynda A et al Primary Care Detection of Chronic Kidney Disease in Adults with Type-2 Diabetes The ADD-CKD Study (Awareness Detection and Drug Therapy in Type-2 Diabetes and Chronic Kidney Disease) PLOS One - In press (2014)
0204060
CKD Screening in Primary Care( of patients)
of Patients
Improved Diagnosis of CKDIn Diabetic Patients
Studies demonstrate that clinician behavior changes when CKD diagnosis improves Significant improvements realized in1-3
bull Increased urinary albumin testing
bull Increased appropriate use of ACEi or ARBs
bull Avoidance of NSAIDs prescribing among patients with low proteinuria ampor eGFR
bull Appropriate nephrology consultation
1 Wei L et al Kidney Int 201384174-1782 Chan M et al Am J Med 20071201063-10703 Fink J et al Am J Kidney Dis 200953681-668
Plan
What is the Pathophysiology of CKD
Pathophysiology of CKD
Risk Factors and Causes for CKD
Pathophysiology of CKD
Stage I amp II CKDDiminished Renal Reserve
eGFR 50
eGFR
Proteinuria
Glomerulosclerosis
ImpairedSluggish Blood Flow
Modifiable Factors-DM-Hypertension-Increase Protein amp Fat intake-Smoking-Use of NSAIDS
Non-Modifiable Factors-Heriditary-Age greater than 60 yrs old-Gender-Race
Thickening ampor an in the amount of collagen in the
basement membranes of the small vessels
Pathophysiology of CKD
Pathophysiological Events Underlying the Origin and Evolution of Hypertensive Nephropathy
Pathogenesis of kidney disease in patients with diabetes
Muskiet M H A et al (2013) Nat Rev Nephrol doi101038nrneph2013272
Pathophysiology of CKD
Pathophysiology of CKD
Pathogenesis of disordered mineral metabolism in CKD
Increase FGF-23
Hypocalcemia
Increase PTH
Bone Disease
Severe inhibition of 1-α hydroxylase and
125 dihydroxyvitamin D
Vit D DeficiencyVit D Resistance
Hyperphosphatemia
Decrease GFR
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Per person per month (PPPM) expenditures during the transition to ESRD by dataset 2011
Incident Medicare (age 67 amp older) amp Truven Health MarketScan (younger than 65) ESRD patients initiating in 2008
USRDS ADR 2013
Preventing progression of CKD will help hold
down costs as the treatment of ESRD is expensive requires
some type of replacement therapy
to maintain life
Relationships between cardiac events and loss of life expectancy resulting from CVD by stage of CKD
Marcello Tonelli et al Circulation 2016133518-536The Lancet Gansevoort et al 2013 Elsevier
Data source Special analyses Medicare 5 percent sample January 1 of each reported year point prevalent Medicare patients age 66 and older Ref 2012 patients Abbreviation CKD chronic kidney disease
All-cause mortality rates (per 1000 patient years at
risk) for Medicare patients aged 66+ by CKD status
and year 2001-2013
Data source Special analyses Medicare 5 percent sample January 1 2013 point prevalent patients aged 66 and older Adj agesexrace Ref all patients 2013 Abbreviations CKD chronic kidney disease CVD
cardiovascular disease DM diabetes mellitus
Adjusted all-cause mortality rates (per 1000 patient years at risk) for Medicare patients aged 66+ by cardiovascular disease and diabetes mellitus CKD status and stage 2013
Cardiovascular Mortality in the General Population and in ESRD Treated by Dialysis
001
100
10
1
01
Annual mortality ()
25ndash34 45ndash54 65ndash74 8535ndash44 55ndash64 75ndash84
MaleFemaleBlackWhite
Dialysis
General population
Age (years)
Am J Kidney Dis 2012 39(S2) S1-246
Data Source National Health and Nutrition Examination Survey (NHANES) 2001-2012 participants aged 20 amp older Abbreviations CKD chronic kidney disease
NHANES participants with CKD aware of their
kidney disease 2001-2012
Gaps in CKD Diagnosis In Diabetic Patients
Szczech Lynda A et al Primary Care Detection of Chronic Kidney Disease in Adults with Type-2 Diabetes The ADD-CKD Study (Awareness Detection and Drug Therapy in Type-2 Diabetes and Chronic Kidney Disease) PLOS One - In press (2014)
0204060
CKD Screening in Primary Care( of patients)
of Patients
Improved Diagnosis of CKDIn Diabetic Patients
Studies demonstrate that clinician behavior changes when CKD diagnosis improves Significant improvements realized in1-3
bull Increased urinary albumin testing
bull Increased appropriate use of ACEi or ARBs
bull Avoidance of NSAIDs prescribing among patients with low proteinuria ampor eGFR
bull Appropriate nephrology consultation
1 Wei L et al Kidney Int 201384174-1782 Chan M et al Am J Med 20071201063-10703 Fink J et al Am J Kidney Dis 200953681-668
Plan
What is the Pathophysiology of CKD
Pathophysiology of CKD
Risk Factors and Causes for CKD
Pathophysiology of CKD
Stage I amp II CKDDiminished Renal Reserve
eGFR 50
eGFR
Proteinuria
Glomerulosclerosis
ImpairedSluggish Blood Flow
Modifiable Factors-DM-Hypertension-Increase Protein amp Fat intake-Smoking-Use of NSAIDS
Non-Modifiable Factors-Heriditary-Age greater than 60 yrs old-Gender-Race
Thickening ampor an in the amount of collagen in the
basement membranes of the small vessels
Pathophysiology of CKD
Pathophysiological Events Underlying the Origin and Evolution of Hypertensive Nephropathy
Pathogenesis of kidney disease in patients with diabetes
Muskiet M H A et al (2013) Nat Rev Nephrol doi101038nrneph2013272
Pathophysiology of CKD
Pathophysiology of CKD
Pathogenesis of disordered mineral metabolism in CKD
Increase FGF-23
Hypocalcemia
Increase PTH
Bone Disease
Severe inhibition of 1-α hydroxylase and
125 dihydroxyvitamin D
Vit D DeficiencyVit D Resistance
Hyperphosphatemia
Decrease GFR
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Relationships between cardiac events and loss of life expectancy resulting from CVD by stage of CKD
Marcello Tonelli et al Circulation 2016133518-536The Lancet Gansevoort et al 2013 Elsevier
Data source Special analyses Medicare 5 percent sample January 1 of each reported year point prevalent Medicare patients age 66 and older Ref 2012 patients Abbreviation CKD chronic kidney disease
All-cause mortality rates (per 1000 patient years at
risk) for Medicare patients aged 66+ by CKD status
and year 2001-2013
Data source Special analyses Medicare 5 percent sample January 1 2013 point prevalent patients aged 66 and older Adj agesexrace Ref all patients 2013 Abbreviations CKD chronic kidney disease CVD
cardiovascular disease DM diabetes mellitus
Adjusted all-cause mortality rates (per 1000 patient years at risk) for Medicare patients aged 66+ by cardiovascular disease and diabetes mellitus CKD status and stage 2013
Cardiovascular Mortality in the General Population and in ESRD Treated by Dialysis
001
100
10
1
01
Annual mortality ()
25ndash34 45ndash54 65ndash74 8535ndash44 55ndash64 75ndash84
MaleFemaleBlackWhite
Dialysis
General population
Age (years)
Am J Kidney Dis 2012 39(S2) S1-246
Data Source National Health and Nutrition Examination Survey (NHANES) 2001-2012 participants aged 20 amp older Abbreviations CKD chronic kidney disease
NHANES participants with CKD aware of their
kidney disease 2001-2012
Gaps in CKD Diagnosis In Diabetic Patients
Szczech Lynda A et al Primary Care Detection of Chronic Kidney Disease in Adults with Type-2 Diabetes The ADD-CKD Study (Awareness Detection and Drug Therapy in Type-2 Diabetes and Chronic Kidney Disease) PLOS One - In press (2014)
0204060
CKD Screening in Primary Care( of patients)
of Patients
Improved Diagnosis of CKDIn Diabetic Patients
Studies demonstrate that clinician behavior changes when CKD diagnosis improves Significant improvements realized in1-3
bull Increased urinary albumin testing
bull Increased appropriate use of ACEi or ARBs
bull Avoidance of NSAIDs prescribing among patients with low proteinuria ampor eGFR
bull Appropriate nephrology consultation
1 Wei L et al Kidney Int 201384174-1782 Chan M et al Am J Med 20071201063-10703 Fink J et al Am J Kidney Dis 200953681-668
Plan
What is the Pathophysiology of CKD
Pathophysiology of CKD
Risk Factors and Causes for CKD
Pathophysiology of CKD
Stage I amp II CKDDiminished Renal Reserve
eGFR 50
eGFR
Proteinuria
Glomerulosclerosis
ImpairedSluggish Blood Flow
Modifiable Factors-DM-Hypertension-Increase Protein amp Fat intake-Smoking-Use of NSAIDS
Non-Modifiable Factors-Heriditary-Age greater than 60 yrs old-Gender-Race
Thickening ampor an in the amount of collagen in the
basement membranes of the small vessels
Pathophysiology of CKD
Pathophysiological Events Underlying the Origin and Evolution of Hypertensive Nephropathy
Pathogenesis of kidney disease in patients with diabetes
Muskiet M H A et al (2013) Nat Rev Nephrol doi101038nrneph2013272
Pathophysiology of CKD
Pathophysiology of CKD
Pathogenesis of disordered mineral metabolism in CKD
Increase FGF-23
Hypocalcemia
Increase PTH
Bone Disease
Severe inhibition of 1-α hydroxylase and
125 dihydroxyvitamin D
Vit D DeficiencyVit D Resistance
Hyperphosphatemia
Decrease GFR
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Data source Special analyses Medicare 5 percent sample January 1 of each reported year point prevalent Medicare patients age 66 and older Ref 2012 patients Abbreviation CKD chronic kidney disease
All-cause mortality rates (per 1000 patient years at
risk) for Medicare patients aged 66+ by CKD status
and year 2001-2013
Data source Special analyses Medicare 5 percent sample January 1 2013 point prevalent patients aged 66 and older Adj agesexrace Ref all patients 2013 Abbreviations CKD chronic kidney disease CVD
cardiovascular disease DM diabetes mellitus
Adjusted all-cause mortality rates (per 1000 patient years at risk) for Medicare patients aged 66+ by cardiovascular disease and diabetes mellitus CKD status and stage 2013
Cardiovascular Mortality in the General Population and in ESRD Treated by Dialysis
001
100
10
1
01
Annual mortality ()
25ndash34 45ndash54 65ndash74 8535ndash44 55ndash64 75ndash84
MaleFemaleBlackWhite
Dialysis
General population
Age (years)
Am J Kidney Dis 2012 39(S2) S1-246
Data Source National Health and Nutrition Examination Survey (NHANES) 2001-2012 participants aged 20 amp older Abbreviations CKD chronic kidney disease
NHANES participants with CKD aware of their
kidney disease 2001-2012
Gaps in CKD Diagnosis In Diabetic Patients
Szczech Lynda A et al Primary Care Detection of Chronic Kidney Disease in Adults with Type-2 Diabetes The ADD-CKD Study (Awareness Detection and Drug Therapy in Type-2 Diabetes and Chronic Kidney Disease) PLOS One - In press (2014)
0204060
CKD Screening in Primary Care( of patients)
of Patients
Improved Diagnosis of CKDIn Diabetic Patients
Studies demonstrate that clinician behavior changes when CKD diagnosis improves Significant improvements realized in1-3
bull Increased urinary albumin testing
bull Increased appropriate use of ACEi or ARBs
bull Avoidance of NSAIDs prescribing among patients with low proteinuria ampor eGFR
bull Appropriate nephrology consultation
1 Wei L et al Kidney Int 201384174-1782 Chan M et al Am J Med 20071201063-10703 Fink J et al Am J Kidney Dis 200953681-668
Plan
What is the Pathophysiology of CKD
Pathophysiology of CKD
Risk Factors and Causes for CKD
Pathophysiology of CKD
Stage I amp II CKDDiminished Renal Reserve
eGFR 50
eGFR
Proteinuria
Glomerulosclerosis
ImpairedSluggish Blood Flow
Modifiable Factors-DM-Hypertension-Increase Protein amp Fat intake-Smoking-Use of NSAIDS
Non-Modifiable Factors-Heriditary-Age greater than 60 yrs old-Gender-Race
Thickening ampor an in the amount of collagen in the
basement membranes of the small vessels
Pathophysiology of CKD
Pathophysiological Events Underlying the Origin and Evolution of Hypertensive Nephropathy
Pathogenesis of kidney disease in patients with diabetes
Muskiet M H A et al (2013) Nat Rev Nephrol doi101038nrneph2013272
Pathophysiology of CKD
Pathophysiology of CKD
Pathogenesis of disordered mineral metabolism in CKD
Increase FGF-23
Hypocalcemia
Increase PTH
Bone Disease
Severe inhibition of 1-α hydroxylase and
125 dihydroxyvitamin D
Vit D DeficiencyVit D Resistance
Hyperphosphatemia
Decrease GFR
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Data source Special analyses Medicare 5 percent sample January 1 2013 point prevalent patients aged 66 and older Adj agesexrace Ref all patients 2013 Abbreviations CKD chronic kidney disease CVD
cardiovascular disease DM diabetes mellitus
Adjusted all-cause mortality rates (per 1000 patient years at risk) for Medicare patients aged 66+ by cardiovascular disease and diabetes mellitus CKD status and stage 2013
Cardiovascular Mortality in the General Population and in ESRD Treated by Dialysis
001
100
10
1
01
Annual mortality ()
25ndash34 45ndash54 65ndash74 8535ndash44 55ndash64 75ndash84
MaleFemaleBlackWhite
Dialysis
General population
Age (years)
Am J Kidney Dis 2012 39(S2) S1-246
Data Source National Health and Nutrition Examination Survey (NHANES) 2001-2012 participants aged 20 amp older Abbreviations CKD chronic kidney disease
NHANES participants with CKD aware of their
kidney disease 2001-2012
Gaps in CKD Diagnosis In Diabetic Patients
Szczech Lynda A et al Primary Care Detection of Chronic Kidney Disease in Adults with Type-2 Diabetes The ADD-CKD Study (Awareness Detection and Drug Therapy in Type-2 Diabetes and Chronic Kidney Disease) PLOS One - In press (2014)
0204060
CKD Screening in Primary Care( of patients)
of Patients
Improved Diagnosis of CKDIn Diabetic Patients
Studies demonstrate that clinician behavior changes when CKD diagnosis improves Significant improvements realized in1-3
bull Increased urinary albumin testing
bull Increased appropriate use of ACEi or ARBs
bull Avoidance of NSAIDs prescribing among patients with low proteinuria ampor eGFR
bull Appropriate nephrology consultation
1 Wei L et al Kidney Int 201384174-1782 Chan M et al Am J Med 20071201063-10703 Fink J et al Am J Kidney Dis 200953681-668
Plan
What is the Pathophysiology of CKD
Pathophysiology of CKD
Risk Factors and Causes for CKD
Pathophysiology of CKD
Stage I amp II CKDDiminished Renal Reserve
eGFR 50
eGFR
Proteinuria
Glomerulosclerosis
ImpairedSluggish Blood Flow
Modifiable Factors-DM-Hypertension-Increase Protein amp Fat intake-Smoking-Use of NSAIDS
Non-Modifiable Factors-Heriditary-Age greater than 60 yrs old-Gender-Race
Thickening ampor an in the amount of collagen in the
basement membranes of the small vessels
Pathophysiology of CKD
Pathophysiological Events Underlying the Origin and Evolution of Hypertensive Nephropathy
Pathogenesis of kidney disease in patients with diabetes
Muskiet M H A et al (2013) Nat Rev Nephrol doi101038nrneph2013272
Pathophysiology of CKD
Pathophysiology of CKD
Pathogenesis of disordered mineral metabolism in CKD
Increase FGF-23
Hypocalcemia
Increase PTH
Bone Disease
Severe inhibition of 1-α hydroxylase and
125 dihydroxyvitamin D
Vit D DeficiencyVit D Resistance
Hyperphosphatemia
Decrease GFR
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Cardiovascular Mortality in the General Population and in ESRD Treated by Dialysis
001
100
10
1
01
Annual mortality ()
25ndash34 45ndash54 65ndash74 8535ndash44 55ndash64 75ndash84
MaleFemaleBlackWhite
Dialysis
General population
Age (years)
Am J Kidney Dis 2012 39(S2) S1-246
Data Source National Health and Nutrition Examination Survey (NHANES) 2001-2012 participants aged 20 amp older Abbreviations CKD chronic kidney disease
NHANES participants with CKD aware of their
kidney disease 2001-2012
Gaps in CKD Diagnosis In Diabetic Patients
Szczech Lynda A et al Primary Care Detection of Chronic Kidney Disease in Adults with Type-2 Diabetes The ADD-CKD Study (Awareness Detection and Drug Therapy in Type-2 Diabetes and Chronic Kidney Disease) PLOS One - In press (2014)
0204060
CKD Screening in Primary Care( of patients)
of Patients
Improved Diagnosis of CKDIn Diabetic Patients
Studies demonstrate that clinician behavior changes when CKD diagnosis improves Significant improvements realized in1-3
bull Increased urinary albumin testing
bull Increased appropriate use of ACEi or ARBs
bull Avoidance of NSAIDs prescribing among patients with low proteinuria ampor eGFR
bull Appropriate nephrology consultation
1 Wei L et al Kidney Int 201384174-1782 Chan M et al Am J Med 20071201063-10703 Fink J et al Am J Kidney Dis 200953681-668
Plan
What is the Pathophysiology of CKD
Pathophysiology of CKD
Risk Factors and Causes for CKD
Pathophysiology of CKD
Stage I amp II CKDDiminished Renal Reserve
eGFR 50
eGFR
Proteinuria
Glomerulosclerosis
ImpairedSluggish Blood Flow
Modifiable Factors-DM-Hypertension-Increase Protein amp Fat intake-Smoking-Use of NSAIDS
Non-Modifiable Factors-Heriditary-Age greater than 60 yrs old-Gender-Race
Thickening ampor an in the amount of collagen in the
basement membranes of the small vessels
Pathophysiology of CKD
Pathophysiological Events Underlying the Origin and Evolution of Hypertensive Nephropathy
Pathogenesis of kidney disease in patients with diabetes
Muskiet M H A et al (2013) Nat Rev Nephrol doi101038nrneph2013272
Pathophysiology of CKD
Pathophysiology of CKD
Pathogenesis of disordered mineral metabolism in CKD
Increase FGF-23
Hypocalcemia
Increase PTH
Bone Disease
Severe inhibition of 1-α hydroxylase and
125 dihydroxyvitamin D
Vit D DeficiencyVit D Resistance
Hyperphosphatemia
Decrease GFR
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Data Source National Health and Nutrition Examination Survey (NHANES) 2001-2012 participants aged 20 amp older Abbreviations CKD chronic kidney disease
NHANES participants with CKD aware of their
kidney disease 2001-2012
Gaps in CKD Diagnosis In Diabetic Patients
Szczech Lynda A et al Primary Care Detection of Chronic Kidney Disease in Adults with Type-2 Diabetes The ADD-CKD Study (Awareness Detection and Drug Therapy in Type-2 Diabetes and Chronic Kidney Disease) PLOS One - In press (2014)
0204060
CKD Screening in Primary Care( of patients)
of Patients
Improved Diagnosis of CKDIn Diabetic Patients
Studies demonstrate that clinician behavior changes when CKD diagnosis improves Significant improvements realized in1-3
bull Increased urinary albumin testing
bull Increased appropriate use of ACEi or ARBs
bull Avoidance of NSAIDs prescribing among patients with low proteinuria ampor eGFR
bull Appropriate nephrology consultation
1 Wei L et al Kidney Int 201384174-1782 Chan M et al Am J Med 20071201063-10703 Fink J et al Am J Kidney Dis 200953681-668
Plan
What is the Pathophysiology of CKD
Pathophysiology of CKD
Risk Factors and Causes for CKD
Pathophysiology of CKD
Stage I amp II CKDDiminished Renal Reserve
eGFR 50
eGFR
Proteinuria
Glomerulosclerosis
ImpairedSluggish Blood Flow
Modifiable Factors-DM-Hypertension-Increase Protein amp Fat intake-Smoking-Use of NSAIDS
Non-Modifiable Factors-Heriditary-Age greater than 60 yrs old-Gender-Race
Thickening ampor an in the amount of collagen in the
basement membranes of the small vessels
Pathophysiology of CKD
Pathophysiological Events Underlying the Origin and Evolution of Hypertensive Nephropathy
Pathogenesis of kidney disease in patients with diabetes
Muskiet M H A et al (2013) Nat Rev Nephrol doi101038nrneph2013272
Pathophysiology of CKD
Pathophysiology of CKD
Pathogenesis of disordered mineral metabolism in CKD
Increase FGF-23
Hypocalcemia
Increase PTH
Bone Disease
Severe inhibition of 1-α hydroxylase and
125 dihydroxyvitamin D
Vit D DeficiencyVit D Resistance
Hyperphosphatemia
Decrease GFR
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Gaps in CKD Diagnosis In Diabetic Patients
Szczech Lynda A et al Primary Care Detection of Chronic Kidney Disease in Adults with Type-2 Diabetes The ADD-CKD Study (Awareness Detection and Drug Therapy in Type-2 Diabetes and Chronic Kidney Disease) PLOS One - In press (2014)
0204060
CKD Screening in Primary Care( of patients)
of Patients
Improved Diagnosis of CKDIn Diabetic Patients
Studies demonstrate that clinician behavior changes when CKD diagnosis improves Significant improvements realized in1-3
bull Increased urinary albumin testing
bull Increased appropriate use of ACEi or ARBs
bull Avoidance of NSAIDs prescribing among patients with low proteinuria ampor eGFR
bull Appropriate nephrology consultation
1 Wei L et al Kidney Int 201384174-1782 Chan M et al Am J Med 20071201063-10703 Fink J et al Am J Kidney Dis 200953681-668
Plan
What is the Pathophysiology of CKD
Pathophysiology of CKD
Risk Factors and Causes for CKD
Pathophysiology of CKD
Stage I amp II CKDDiminished Renal Reserve
eGFR 50
eGFR
Proteinuria
Glomerulosclerosis
ImpairedSluggish Blood Flow
Modifiable Factors-DM-Hypertension-Increase Protein amp Fat intake-Smoking-Use of NSAIDS
Non-Modifiable Factors-Heriditary-Age greater than 60 yrs old-Gender-Race
Thickening ampor an in the amount of collagen in the
basement membranes of the small vessels
Pathophysiology of CKD
Pathophysiological Events Underlying the Origin and Evolution of Hypertensive Nephropathy
Pathogenesis of kidney disease in patients with diabetes
Muskiet M H A et al (2013) Nat Rev Nephrol doi101038nrneph2013272
Pathophysiology of CKD
Pathophysiology of CKD
Pathogenesis of disordered mineral metabolism in CKD
Increase FGF-23
Hypocalcemia
Increase PTH
Bone Disease
Severe inhibition of 1-α hydroxylase and
125 dihydroxyvitamin D
Vit D DeficiencyVit D Resistance
Hyperphosphatemia
Decrease GFR
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Improved Diagnosis of CKDIn Diabetic Patients
Studies demonstrate that clinician behavior changes when CKD diagnosis improves Significant improvements realized in1-3
bull Increased urinary albumin testing
bull Increased appropriate use of ACEi or ARBs
bull Avoidance of NSAIDs prescribing among patients with low proteinuria ampor eGFR
bull Appropriate nephrology consultation
1 Wei L et al Kidney Int 201384174-1782 Chan M et al Am J Med 20071201063-10703 Fink J et al Am J Kidney Dis 200953681-668
Plan
What is the Pathophysiology of CKD
Pathophysiology of CKD
Risk Factors and Causes for CKD
Pathophysiology of CKD
Stage I amp II CKDDiminished Renal Reserve
eGFR 50
eGFR
Proteinuria
Glomerulosclerosis
ImpairedSluggish Blood Flow
Modifiable Factors-DM-Hypertension-Increase Protein amp Fat intake-Smoking-Use of NSAIDS
Non-Modifiable Factors-Heriditary-Age greater than 60 yrs old-Gender-Race
Thickening ampor an in the amount of collagen in the
basement membranes of the small vessels
Pathophysiology of CKD
Pathophysiological Events Underlying the Origin and Evolution of Hypertensive Nephropathy
Pathogenesis of kidney disease in patients with diabetes
Muskiet M H A et al (2013) Nat Rev Nephrol doi101038nrneph2013272
Pathophysiology of CKD
Pathophysiology of CKD
Pathogenesis of disordered mineral metabolism in CKD
Increase FGF-23
Hypocalcemia
Increase PTH
Bone Disease
Severe inhibition of 1-α hydroxylase and
125 dihydroxyvitamin D
Vit D DeficiencyVit D Resistance
Hyperphosphatemia
Decrease GFR
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Plan
What is the Pathophysiology of CKD
Pathophysiology of CKD
Risk Factors and Causes for CKD
Pathophysiology of CKD
Stage I amp II CKDDiminished Renal Reserve
eGFR 50
eGFR
Proteinuria
Glomerulosclerosis
ImpairedSluggish Blood Flow
Modifiable Factors-DM-Hypertension-Increase Protein amp Fat intake-Smoking-Use of NSAIDS
Non-Modifiable Factors-Heriditary-Age greater than 60 yrs old-Gender-Race
Thickening ampor an in the amount of collagen in the
basement membranes of the small vessels
Pathophysiology of CKD
Pathophysiological Events Underlying the Origin and Evolution of Hypertensive Nephropathy
Pathogenesis of kidney disease in patients with diabetes
Muskiet M H A et al (2013) Nat Rev Nephrol doi101038nrneph2013272
Pathophysiology of CKD
Pathophysiology of CKD
Pathogenesis of disordered mineral metabolism in CKD
Increase FGF-23
Hypocalcemia
Increase PTH
Bone Disease
Severe inhibition of 1-α hydroxylase and
125 dihydroxyvitamin D
Vit D DeficiencyVit D Resistance
Hyperphosphatemia
Decrease GFR
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Pathophysiology of CKD
Risk Factors and Causes for CKD
Pathophysiology of CKD
Stage I amp II CKDDiminished Renal Reserve
eGFR 50
eGFR
Proteinuria
Glomerulosclerosis
ImpairedSluggish Blood Flow
Modifiable Factors-DM-Hypertension-Increase Protein amp Fat intake-Smoking-Use of NSAIDS
Non-Modifiable Factors-Heriditary-Age greater than 60 yrs old-Gender-Race
Thickening ampor an in the amount of collagen in the
basement membranes of the small vessels
Pathophysiology of CKD
Pathophysiological Events Underlying the Origin and Evolution of Hypertensive Nephropathy
Pathogenesis of kidney disease in patients with diabetes
Muskiet M H A et al (2013) Nat Rev Nephrol doi101038nrneph2013272
Pathophysiology of CKD
Pathophysiology of CKD
Pathogenesis of disordered mineral metabolism in CKD
Increase FGF-23
Hypocalcemia
Increase PTH
Bone Disease
Severe inhibition of 1-α hydroxylase and
125 dihydroxyvitamin D
Vit D DeficiencyVit D Resistance
Hyperphosphatemia
Decrease GFR
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Risk Factors and Causes for CKD
Pathophysiology of CKD
Stage I amp II CKDDiminished Renal Reserve
eGFR 50
eGFR
Proteinuria
Glomerulosclerosis
ImpairedSluggish Blood Flow
Modifiable Factors-DM-Hypertension-Increase Protein amp Fat intake-Smoking-Use of NSAIDS
Non-Modifiable Factors-Heriditary-Age greater than 60 yrs old-Gender-Race
Thickening ampor an in the amount of collagen in the
basement membranes of the small vessels
Pathophysiology of CKD
Pathophysiological Events Underlying the Origin and Evolution of Hypertensive Nephropathy
Pathogenesis of kidney disease in patients with diabetes
Muskiet M H A et al (2013) Nat Rev Nephrol doi101038nrneph2013272
Pathophysiology of CKD
Pathophysiology of CKD
Pathogenesis of disordered mineral metabolism in CKD
Increase FGF-23
Hypocalcemia
Increase PTH
Bone Disease
Severe inhibition of 1-α hydroxylase and
125 dihydroxyvitamin D
Vit D DeficiencyVit D Resistance
Hyperphosphatemia
Decrease GFR
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Pathophysiology of CKD
Stage I amp II CKDDiminished Renal Reserve
eGFR 50
eGFR
Proteinuria
Glomerulosclerosis
ImpairedSluggish Blood Flow
Modifiable Factors-DM-Hypertension-Increase Protein amp Fat intake-Smoking-Use of NSAIDS
Non-Modifiable Factors-Heriditary-Age greater than 60 yrs old-Gender-Race
Thickening ampor an in the amount of collagen in the
basement membranes of the small vessels
Pathophysiology of CKD
Pathophysiological Events Underlying the Origin and Evolution of Hypertensive Nephropathy
Pathogenesis of kidney disease in patients with diabetes
Muskiet M H A et al (2013) Nat Rev Nephrol doi101038nrneph2013272
Pathophysiology of CKD
Pathophysiology of CKD
Pathogenesis of disordered mineral metabolism in CKD
Increase FGF-23
Hypocalcemia
Increase PTH
Bone Disease
Severe inhibition of 1-α hydroxylase and
125 dihydroxyvitamin D
Vit D DeficiencyVit D Resistance
Hyperphosphatemia
Decrease GFR
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Pathophysiology of CKD
Pathophysiological Events Underlying the Origin and Evolution of Hypertensive Nephropathy
Pathogenesis of kidney disease in patients with diabetes
Muskiet M H A et al (2013) Nat Rev Nephrol doi101038nrneph2013272
Pathophysiology of CKD
Pathophysiology of CKD
Pathogenesis of disordered mineral metabolism in CKD
Increase FGF-23
Hypocalcemia
Increase PTH
Bone Disease
Severe inhibition of 1-α hydroxylase and
125 dihydroxyvitamin D
Vit D DeficiencyVit D Resistance
Hyperphosphatemia
Decrease GFR
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Pathophysiological Events Underlying the Origin and Evolution of Hypertensive Nephropathy
Pathogenesis of kidney disease in patients with diabetes
Muskiet M H A et al (2013) Nat Rev Nephrol doi101038nrneph2013272
Pathophysiology of CKD
Pathophysiology of CKD
Pathogenesis of disordered mineral metabolism in CKD
Increase FGF-23
Hypocalcemia
Increase PTH
Bone Disease
Severe inhibition of 1-α hydroxylase and
125 dihydroxyvitamin D
Vit D DeficiencyVit D Resistance
Hyperphosphatemia
Decrease GFR
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Pathogenesis of kidney disease in patients with diabetes
Muskiet M H A et al (2013) Nat Rev Nephrol doi101038nrneph2013272
Pathophysiology of CKD
Pathophysiology of CKD
Pathogenesis of disordered mineral metabolism in CKD
Increase FGF-23
Hypocalcemia
Increase PTH
Bone Disease
Severe inhibition of 1-α hydroxylase and
125 dihydroxyvitamin D
Vit D DeficiencyVit D Resistance
Hyperphosphatemia
Decrease GFR
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Pathophysiology of CKD
Pathophysiology of CKD
Pathogenesis of disordered mineral metabolism in CKD
Increase FGF-23
Hypocalcemia
Increase PTH
Bone Disease
Severe inhibition of 1-α hydroxylase and
125 dihydroxyvitamin D
Vit D DeficiencyVit D Resistance
Hyperphosphatemia
Decrease GFR
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Pathophysiology of CKD
Pathogenesis of disordered mineral metabolism in CKD
Increase FGF-23
Hypocalcemia
Increase PTH
Bone Disease
Severe inhibition of 1-α hydroxylase and
125 dihydroxyvitamin D
Vit D DeficiencyVit D Resistance
Hyperphosphatemia
Decrease GFR
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Pathogenesis of disordered mineral metabolism in CKD
Increase FGF-23
Hypocalcemia
Increase PTH
Bone Disease
Severe inhibition of 1-α hydroxylase and
125 dihydroxyvitamin D
Vit D DeficiencyVit D Resistance
Hyperphosphatemia
Decrease GFR
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Pathogenesis of disordered mineral metabolism in CKD
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Self-perpetuating triad formed by the interactions among anemia chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each
other and translate into mortality multipliers
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Optimal anemia management reduces CV morbidity mortality and costs in CKD
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Madhumathi Rao Brian JG Pereira Kidney International Volume 68 Issue 4 2005 1432ndash1438
Mechanisms of Anemia in CKD
1048707 EPO deficiency1048707 Blood loss1048707 Shorter RBC life span1048707 Decreased bone marrow responsiveness to EPO1048707 Vitamin deficiencies1048707 Iron deficiency (poor iron absorption)1048707 High uremia level1048707 Intoxication impairing RBC development (Aluminium)1048707 Hemolysis (copper chloramines)1048707 Chronic inflammation
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Data Source Special analyses Medicare 5 percent sample Patients aged 66 and older alive without end-stage renal disease and residing in the US on 12312013 with fee-for-service coverage for the entire
calendar year Totals of patients for the study cohort N=1238888 With CKD=132840 Without CKD=1106048 Abbreviations AFIB atrial fibrillation AMI acute myocardial infarction ASHD atherosclerotic heart
disease CHF congestive heart failure CKD chronic kidney disease CVATIA cerebrovascular accidenttransient ischemic attack CVD cardiovascular disease PAD peripheral arterial disease SCAVA sudden
cardiac arrest and ventricular arrhythmias VHD valvular heart disease
Cardiovascular disease in patients
with or without CKD 2013
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Proposed feedback loops in cardiorenal syndrome (CRS)
Marcello Tonelli et al Circulation 2016133518-536
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Pathophysiology and definitions of the five subtypes of CRS
Claudio Ronco et al Eur Heart J 201031703-711
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Hyperlipidemia (Role )
middot Hyperlipidemia common in CRF- especially in Nephrotic Syndrome
middot Excessive lipids accelerate progression of renal disease
middot Cholesterol increases glomerular injury
middot Two known paths of hyperlipidemia progression in CRFmiddot Hyperlipidemia activates LDL receptors in mesangial cellsmiddot Increased synthesis of lipoproteins in the liver related to
increased albumin production
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Inflammation (Role )
middot Inflammatory response can be triggered by tissue injury infections toxins immune responses andor Angiotensin II
middot Can be acute or chronicmiddot Can affect the renal pelvis and
interstitial tissue as in pyelonephritis
middot Can affect the glomeruli as in glomerulonephritis
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
CKD prolongs inflammatory reactions
Causes of Inflammation in CRF middot Infectionmiddot Anemiamiddot Uremia ndash increases oxidation of
proteins lipids amp carbohydrates leading to vascular inflammation
middot Malnutrition ndash decreases antioxidants
middot Low serum albumin ndash decreases antioxidants
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Inflammation- (Cont)
middot Adverse effects of chronic inflammationmiddot Decreased appetitemiddot Muscle and fat wastingmiddot Endothelial damagemiddot Atherosclerosismiddot Hypoalbuminemiamiddot Increased cardiovascular disease risk
Legg V(2005) Complications of chronic kidney disease AJN105(6)40-50
middot Angio-II is an Inflammatory mediator causingbull Increased vascular permeabilitybull Increased leukocyte infiltration (monocytes macrophages)bull Cell proliferation amp hypertrophy
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Genetic Considerations
middot Autosomal dominant Polycystic Kidney Disease
middot Alportrsquos hereditary nephritis
middot Familial FSGS
middot Nephronopthisis Nephropathic Cystinosis
(Fanconirsquos Syndrome)
middot Medullary cystic kidney disease
middot Fabryrsquos disease
Sanford R (2004) Autosomal dominant polycystic kidney disease Retrieved February 8 2006
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Polycystic Kidney Disease
middot Most Common Genetic Disordermiddot Numerous fluid-filled cysts in kidneys and renal
tubulesmiddot Normal renal tissue replaced by cystsmiddot Decreased function leads to ESRD
Two Major Forms of PKDmiddot Autosomal Dominant PKD (90)
middot Occurs equally males and females mainly Caucasiansmiddot One parent with ADPKD gene = 50 chance children
will inherit diseasemiddot Gene mutation on chromosome 16 or 4
middot Autosomal Recessive PKD (10)middot 1 in 4 babies (of parents with mutation)middot Mutation on chromosome 6 Only treatment for both when arrived to
ESRD = dialysis and kidney transplantation
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Risk Factors for CKD
Risk Factor Definition Examples
Susceptibility factors
Increase susceptibility to kidney damage
Older age Family HO CKD Reduction in kidney mass Low Birthweight Low income or education
Initiation Factors
Directly initiate kidney damage DM HTN Autoimmune Diseases Systemic Infections Urinary Stones Lower UT Obstruction Drug Toxicity
Progression Factors
Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage
Higher Level of Proteinuria Higher BP Poor Glycemic Control Smoking
ESRD Increase morbidity and mortality in kidney failure
Lowe Dialysis Dose (KTV) Temporary Vascular Access Low Serum Albumin Level Late Referal
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Plan
How should clinicians estimate the stage of CKD
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
2 simple tests will identify CKD in adults
middot eGFR - Estimated GFR from serum creatinine using a certain equation
middot UACR - Urine albumin to creatinine ratio on a ldquospotrdquo urine sample
middot 24-hour urine collections are NOT needed
-Diabetics should be tested once a year Others at risk can be tested less frequently as long as normal
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
How should clinicians estimate GFR and the stage of CKD
MDRD equationmiddot GFR (mLmin per 173 m2)= 1863 times (Scr mgdL)minus1154 times ageminus0203 times (1210
if black) times (0742 if female)
CKD-EPI equationGFR = 141 times minimum(Scrκ 1)α times maximum(Scrκ 1)-1209 times 0993Age times (1018 if female) times (1159 if black)
Cockcroft-GaultMen CrCl (mLmin) = (140 - age) x wt (kg) SCr x 081Women multiply by 085
Scr is serum creatinine κ is 07 for females and 09 for males α is -0329 for females and -0411 for males minimum indicates the minimum of Scrκ or 1
maximum indicates the maximum of Scrκ or 1
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
NICE Stages of CKDCKD Stage Description (eGFR mlmin173m2)
Stage 1 Normal eGFR (gt90)With other evidence of kidney damage
Stage 2 eGFR 60 ndash 90With other evidence of kidney damage
Stage 3aStage 3b
eGFR 45-59eGFR 30-44
Stage 4 eGFR 15 ndash 29
Stage 5 eGFR lt 15 Evidence of chronic kidney damage includes persistent microalbuminuria or proteinuria haematuria structural abnormalities biopsy proven glomerulonephritis
KDOQI CKD Classification
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
24-yoBlack Man
63-yo White Man
59-yo White
Woman
S Cr 13 mgdL 13 mgdL 13 mgdL
GFR as estimated by CKD-
EPI Study equation
66 mLmin173 m2
45 mLmin173 m2
55 mLmin173 m2
The perils of using serum creatinine to ldquoguessrdquo level of renal function
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012)
Stage Description GFR (mlmin173 m2)
PrevalenceN
(1000s)
1 Kidney Damage with Normal or GFR 90 5900 33
2 Kidney Damage with Mild GFR 60-89 5300 30
3 Moderate GFR 30-59 7600 43
4 Severe GFR 15-29 400 02
5 Kidney Failure lt 15 or Dialysis 300 01
Stages 1-4 from NHANES III (1988-2008) Population of 177 million with age 20 Stage 5 from USRDS (2012) includes approximately 230000 patients treated by dialysis and assuming 70000 additional patients not on dialysis GFR estimated from serum creatinine using MDRD Study equation based on age gender race and calibration for serum creatinine For Stage 1 and 2 kidney damage estimated by spot albumin-to-creatinine ratio 17 mgg in men or 25 mgg in women in two measurements
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Classification of CKD Based on GFR and Albuminuria Categories ldquoHeat Maprdquo
Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group Kidney Int Suppls 201331-150
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Automatic eGFR by the laboratory reporting is best
middot GFR is the accepted measure of kidney function
middot GFR is difficult to infer from serum creatinine alone
middot Automatic reporting identifies CKD patients with apparently ldquonormalrdquo serum creatinine reduces barrier to early detection and identifies people at high risk for contrast agents and other nephrotoxins
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Caveats to eGFR
middot An estimate based on population data not the patientrsquos actual GFR
middot Not reliable when used with patients middot with rapidly changing creatinine levels (eg AKI in
the ICU)middot with extremes in muscle mass eg cachexia or
paraplegia
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Plan
What laboratory tests and imaging should clinicians use to evaluate CKD
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Evaluation for CKD
middot Bloodmiddot CBC with diffmiddot Urea Creatinine and Electrolytes
with Ca2+ and phosphorousmiddot PTHmiddot HBA1c
middot LFTs middot Uric acid middot Fe2+ studies
middot Urinemiddot Urinalysis with microscopymiddot Spot urine for microalbuminmiddot 24-urine collection for protein
and creatinine (if needed)
middot Ultrasound -For hydronephrosis cysts and stones
-To assess echogenicity size kidney symmetry
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
middot If indicated by history or by findingsmiddot Antinuclear antibody to evaluate for lupus and other autoimmune dismiddot Serologies for HBV HCV and HIVmiddot Serum antineutrophil cytoplasmic antibodies for vasculitismiddot Serum and urine protein immunoelectrophoresis for multiple
myeloma
middot Stages 4 and 5 CKD middot test for hyperkalemia acidosis hypocalcemia hyperphosphatemia
Evaluation for CKD (Cont)
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Urine albumin amp protein to creatinine ratio
middot Albumin-to-creatinine ratiomiddot Normal to mildly increased lt30 mggmiddot Moderately increased 30-300 mggmiddot Severely increased gt300 mgg
middot Protein-to-creatinine ratiomiddot Normal to mildly increased lt150 mggmiddot Moderately increased 150-500 mggmiddot Severely increased gt500 mgg
bull Type 2 diabetes screen for albuminuria regularly Positive when gt30 mgg creatinine in a spot urine sample
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Plan
What clinical manifestations should clinicians look for when evaluating
patients for CKD
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Chronic vs Acute Renal Failure
middot Acute Renal Failure (ARF)middot Abrupt onsetmiddot Potentially reversible
middot Chronic Renal Failure (CRF)middot Progresses over at least 3 monthsmiddot Permanent- non-reversible damage to nephrons
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
What clinical manifestations should clinicians look for when evaluating patients for CKD
bull Recent diarrhea bleeding or dehydration may decrease renal perfusion that leads to acute kidney injury
bull A medication history may reveal a drug cause of CKD
bull History of HF or cirrhosis suggests decreased renal perfusion
bull Skin rash arthritis mononeuropathy or systemic symptoms suggests vasculitis including lupus
bull Findings associated with diabetes and hypertension
bull Infection with HBV HCV or HIV may cause proteinuria
bull Family history of kidney disease suggests polycystic disease the Alport syndrome or medullary cystic kidney disease
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Signs amp Symptoms Visual Verbal Clues
middot Dry mouth fatigue nausea ndash dt hyponatremia amp uremiamiddot Hypertension ndash dt sodium amp water retentionmiddot Hypervolemia ndash dt sodium amp water retentionmiddot Grayyellow skin ndash dt accumulated urine pigmentsmiddot Cardiac irritability ndash dt hyperkalemiamiddot Muscle cramps ndash dt hypocalcemiamiddot Bone amp muscle pain ndash dt hypocalcemiahyperphosphatemia middot Restless leg syndrome ndash dt toxinsrsquo effects on the nervous
system
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
middot Check for orthostasismiddot Look for rashes and petechiaemiddot Examine the fundus for diabetic retinopathy or hypertensive
retinopathymiddot Evaluate for heart failuremiddot A renal bruit suggests renal artery stenosis middot Inflamed joints suggest vasculitis or autoimmune processesmiddot Asterixis or encephalopathy suggests uremia
Signs amp Symptoms Visual Verbal Clues
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Manifestations of CKD
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Stages and Clinical Features of Non-Diabetic CKD
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Stages and Clinical Features of Diabetic CKD
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Plan
How should clinicians construct a differential diagnosis of CKD
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
How should clinicians classify CKD and construct a differential diagnosis
middot By GFR and albuminuriamiddot Determine cause based on
middot Presence or absence of systemic disease middot Presumed location of damage in the kidney (glomerular
tubulointerstitial vascular or cystic)
Classify patients with CKD into 1 of 3 broad categoriesDiabetic kidney disease
Hypertensive kidney disease
Non-hypertensive non-diabetic kidney disease
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Classification of CKD by Diagnosis
middot Diabetic Kidney Diseasemiddot Glomerular diseases (autoimmune diseases systemic
infections drugs neoplasia)middot Vascular diseases (renal artery disease hypertension
microangiopathy)middot Tubulointerstitial diseases (urinary tract infection
stones obstruction drug toxicity)middot Cystic diseases (polycystic kidney disease)middot Diseases in the transplant (Allograft nephropathy
drug toxicity recurrent diseases transplant glomerulopathy)
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Identify reversible causes
middot Think about volume contraction urinary obstruction or toxic effects of medications
middot Rxmiddot ACEsARBsmiddot NSAIDsmiddot Aminoglycosides and amphotericin Bmiddot IV Radiocontrast agents
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Plan
When should clinicians consider consulting with a nephrologist for
diagnosing patients with possible CKD
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Nephrology referral suggestions
bull Regardless of when you refer
bull Obtaining preliminary evaluation (eg ultrasound screening serologies)
bull Providing consultant with patient history including serial measures of renal function
bull To assist with diagnostic challenge (eg decision to biopsy)
bull To assist with therapeutic challenge (eg blood pressure or immunosuppression)
bull Preparation for renal replacement therapy especially when GFR less than 30
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Significant albuminuria is defined as ACR ge300 mgg (ge30 mgmmol) or AER ge300 mg24 hours approximately equivalent to PCR ge500 mgg (ge50 mgmmol) or PER ge500 mg24 hours Progression of CKD is defined as one or more of the following 1) A decline in GFR category accompanied by a 25 or greater drop in eGFR from baseline andor 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5mlmin173m2year KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services for People with CKD
bull Acute kidney injury or abrupt sustained fall in GFRbull GFR lt30 mlmin173m2 (GFR categories G4-G5)bull Persistent albuminuria (ACR gt 300 mgg)bull Atypical Progression of CKD bull Urinary red cell casts RBC more than 20 per HPF sustained and not readily
explainedbull Hypertension refractory to treatment with 4 or more antihypertensive
agentsbull Persistent abnormalities of serum potassiumbull Recurrent or extensive nephrolithiasisbull Hereditary kidney diseasebull No clear etiology of CKDbull Type 2 diabetes with proteinuria wo coexistent retinopathy or neuropathy bull Rapid decline in kidney function (gt5 mLmin per 173 m2 per year)
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Observational Studies of Early vs Late Nephrology Consultation
Chan M et al Am J Med 20071201063-1070KDIGO CKD Work Group Kidney Int Suppls 201331-150
Variable Early Referral Mean (SD)
Late Referral Mean (SD)
P Value
Overall Mortality 11 (3) 23 (4) lt00001
1-Year Mortality 13 (4) 29 (5) 0028
Hospital Length of stay-day
135 (22) 253 (38) 00007
Serum Albumin at start of Dialysis
362 (005) 340 (003) 0001
Hematocrit at start of Dialysis
3054 (018) 2971 (010) 0013
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Plan
How should Clinician Monitor CKD
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Monitoring of CKD
middot Serial measurements ofmiddot Creatininemiddot eGFR
middot Albumin middot Protein-creatinine ratio in the 1st morning samplemiddot Electrolytes including HCO3 Ca Phosph alkaline
phosphatase iron studies intact PTH middot Renal sonogrammiddot Renal biopsy
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Stage of CKD by eGFR and albuminuria categories
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Clinical Practice Guidelines for the Detection Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased risk Test for CKD Risk factor management
1 Kidney
damage with normal or
GFR
gt90
Diagnosis Comorbid conditions
CVD and CVD risk factors
Specific therapy based on diagnosis Management of comorbid conditions
Treatment of CVD and CVD risk factors
2 Kidney
damage with mild GFR
60-89 Rate of progression Slowing rate of loss of kidney function 1
3 Moderate GFR 30-59 Complications Prevention and treatment of complications
4 Severe GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist
5 Kidney Failure lt15 Kidney replacement therapy 1Target blood pressure less than 13080 mm Hg Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mgg
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Plan
Which drugs and other agents cause acute kidney injury in patients with CKD
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Medications and CKD
middot NSAIDS ndash inhibit prostaglandins decreasing GFR and reduced sodium excretionmiddot Decongestants ndash elevate blood-pressure and increase renal damagemiddot Antacids and laxatives containing magnesium amp aluminum causes mineral
accumulation and metabolic complicationsmiddot Herbal Remedies ndash (juniper berry buckthorn bark cascara bark licorice root) can
cause electrolyte imbalances which worsen with diuretic therapymiddot Aminoglycoside antibiotics middot Amphotericin Bmiddot If Radiocontrast Agents essential give
middot sodium bicarbonate or 09 normal saline IV before and after procedure for patients at increased risk for contrast nephropathy
middot Consider N-acetylcysteine before and after radiocontrast only in high-risk patients
middot stop Metformin middot Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for
nephrogenic systemic fibrosis
Campoy S Elwell R(2005) Pharmacology amp CKD AJN 105(9)60-72
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Common Medications Requiring DoseReduction in CKD
middot Allopurinolmiddot Gabapentin
middot CKD 4- Max dose 300mg qdmiddot CKD 5- Max dose 300mg qod
middot Reglanmiddot Reduce 50 for eGFRlt 40middot Can cause irreversible EPS with
chronic usemiddot Narcotics
middot Methadone and fentanyl best for ESRD patients
middot Lowest risk of toxic metabolites
bull Renally cleared beta blockers
o Atenolol bisoprolol nadolol
bull Digoxinbull Some Statins
o Lovastatin pravastatin simvastatin Fluvastatin rosuvastatin
bull Antimicrobialso Antifungals
aminoglycosides Bactrim Macrobid
bull Enoxaparinbull Methotrexatebull Colchicine
Adjust dosing of other medications to avoid other AEs
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Medications in CKD
middot CKD patients at high risk for drug-related adverse eventsmiddot Several classes of drugs renally eliminatedmiddot Consider kidney function and current eGFR (not just SCr) when
prescribing medsmiddot Minimize pill burden as much as possiblemiddot Remind CKD patients to avoid NSAIDsmiddot No Dual RAAS blockade (with exceptions)middot Any med with gt30 renal clearance probably needs dose
adjustment for CKDmiddot No bisphosphonates for eGFR lt30middot Avoid Gadolinium Contrast for eGFR lt30
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Clinical Bottom Line Diagnosis
o CKD is defined as kidney damage or a GFR lt60 mLmin per 173 m2 for gt 3 months
o Classifyo Diabetic nephropathyo Hypertensive nephropathyo Nondiabetic nonhypertensive
kidney diseaseo Then into groups based on
levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires
o Diagnostic tests
o Renal ultrasound
o Sometimes renal biopsy
o Identify risk factorso Know patientrsquos GFR using
appropriate screening toolso Help your patient adjust
medicationo Modify dieto Partner and refer to specialist
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Pathophysiology of CKD-CVD
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Kidneydamage and
normal or GFR
Kidneydamage and
mild GFR
Severe GFR
Kidneyfailure
Moderate GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always) and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the Patient Safety Approach to CKD
Patient safety
Consult
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Chronic Kidney DiseaseAn Update
(Part II)
Yassin Ibrahim El-ShahatConsultant Nephrology amp Hypertension
Chief Medical OfficerBurjeel Hospital Abu Dhabi
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-
Pathophysiology of CKD in DM
Jun Wada and Hirofumi Makino Clin Sci 2013124139-152
- Chronic Kidney Disease An Update (Part I)
- Objectives
- Plan
- Plan (2)
- What is the definition of CKD
- What is the definition of CKD (2)
- CKD as a Public Health Issue
- 26 million Americans have CKD
- Slide 9
- Slide 10
- Slide 11
- Incidence varies widely by race and ethnicity
- Slide 13
- USRDS Incident counts amp adjusted rates by age
- Prevalence of Abnormalities at each level of GFR
- Slide 16
- CKD is disproportionately costly
- Overall expenditures for CKD in the Medicare population age 65
- Slide 19
- Per person per month (PPPM) expenditures during the transition
- Slide 21
- Slide 22
- Slide 23
- Cardiovascular Mortality in the General Population and in ESRD
- Slide 25
- Gaps in CKD Diagnosis In Diabetic Patients
- Slide 27
- Plan (3)
- Pathophysiology of CKD
- Risk Factors and Causes for CKD
- Pathophysiology of CKD (2)
- Pathophysiology of CKD (3)
- Pathophysiological Events Underlying the Origin and Evolution o
- Slide 34
- Pathophysiology of CKD (4)
- Pathophysiology of CKD (5)
- Slide 37
- Slide 38
- Slide 39
- Slide 40
- Slide 41
- Slide 42
- Slide 43
- Hyperlipidemia (Role )
- Inflammation (Role )
- Inflammation- (Cont)
- Genetic Considerations
- Polycystic Kidney Disease
- Risk Factors for CKD
- Plan (4)
- 2 simple tests will identify CKD in adults
- How should clinicians estimate GFR and the stage of CKD
- Slide 53
- The perils of using serum creatinine to ldquoguessrdquo level of renal
- Prevalence of CKD and Estimated Number of Adults with CKD in th
- Classification of CKD Based on GFR and Albuminuria Categories
- Automatic eGFR by the laboratory reporting is best
- Caveats to eGFR
- Plan (5)
- Evaluation for CKD
- Evaluation for CKD (Cont)
- Urine albumin amp protein to creatinine ratio
- Plan (6)
- Chronic vs Acute Renal Failure
- What clinical manifestations should clinicians look for when ev
- Signs amp Symptoms Visual Verbal Clues
- Signs amp Symptoms Visual Verbal Clues (2)
- Manifestations of CKD
- Stages and Clinical Features of Non-Diabetic CKD
- Stages and Clinical Features of Diabetic CKD
- Plan (7)
- How should clinicians classify CKD and construct a differential
- Classification of CKD by Diagnosis
- Identify reversible causes
- Plan (8)
- Nephrology referral suggestions
- Slide 77
- Slide 78
- Plan (9)
- Monitoring of CKD
- Stage of CKD by eGFR and albuminuria categories
- Clinical Practice Guidelines for the Detection Evaluation and
- Plan (10)
- Medications and CKD
- Common Medications Requiring Dose Reduction in CKD
- Medications in CKD
- Clinical Bottom Line Diagnosis
- Pathophysiology of CKD-CVD
- Slide 89
- Chronic Kidney Disease An Update (Part II)
- Slide 91
- Pathophysiology of CKD in DM
-