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Chronic Kidney DiseaseChronic Kidney Disease
RIZKI ALIANA AGUSTINARIZKI ALIANA AGUSTINA
Goals and ObjectivesGoals and Objectives Review the K/DOQI definition and Review the K/DOQI definition and
classification of chronic kidney classification of chronic kidney disease (CKD)disease (CKD)
Review the prevalence and causes Review the prevalence and causes of CKD in the US.of CKD in the US.
Understand the primary evaluation Understand the primary evaluation and management of patients with and management of patients with CKD.CKD.
Defining “CKD”Defining “CKD”
Kidney damage for ≥ 3 months, defined by Kidney damage for ≥ 3 months, defined by structural or functional abnormalities of structural or functional abnormalities of the kidney, with or without decreased GFR, the kidney, with or without decreased GFR, manifest by eithermanifest by either Pathologic abnormalities, orPathologic abnormalities, or Markers of kidney damage, such as Markers of kidney damage, such as
abnormalities of the blood or urine, or in abnormalities of the blood or urine, or in imaging tests imaging tests
GFR < 60 mL/min/1.73 mGFR < 60 mL/min/1.73 m22 for ≥ 3 months for ≥ 3 months with or without kidney damage.with or without kidney damage.
Defining “Kidney Damage”Defining “Kidney Damage”
Pathologic Abnormalities?Pathologic Abnormalities? By Radiology (US, CT, MR, etc)--e.g.By Radiology (US, CT, MR, etc)--e.g.
Multiple cysts consistent with PKDMultiple cysts consistent with PKD Extensive scarringExtensive scarring Small kidneys--but be careful of the term Small kidneys--but be careful of the term
“medical renal disease”.“medical renal disease”. REMEMBER: Renal masses or cysts that are REMEMBER: Renal masses or cysts that are
not simple should be referred to a not simple should be referred to a UROLOGIST!!UROLOGIST!!
By Histology--ie, renal biopsyBy Histology--ie, renal biopsy
Defining “Kidney Damage”Defining “Kidney Damage”
Markers of Kidney Damage?Markers of Kidney Damage? ProteinuriaProteinuria MicroalbuminuriaMicroalbuminuria Hematuria (especially when seen with Hematuria (especially when seen with
proteinuria)proteinuria) Isolated hematuria has a long differential: infection, Isolated hematuria has a long differential: infection,
stone, malignancy, etc.stone, malignancy, etc. Casts (especially with cellular elements)Casts (especially with cellular elements)
Screening for proteinuriaScreening for proteinuriaUrine dipstick for protein
NegativePositive
(Urine protein >300mg/l)On 2 separate occasions(exclude other causes)
Overt NephropathyQuantify excretion rate24HUP
3-6 monthly follow-up of microalbuminuriaOptimise glycaemic controlStrict Bp controlACE/ARBStop smokingLifestyle modificationTreat hyperlipidaemiaAvoid excessive protein intakeMonitor renal functionMonitor other endorgan damage
Screen forMicroalbuminuria(on early morning spot urine)
Negative
Yearly test
Positive
Retest twice in 3-6/12Exclude other cause
If 2 of test are positiveDiagnosis of microalbuminuria Is established
Significance of proteinuriaSignificance of proteinuria A dominant risk factor for deterioration A dominant risk factor for deterioration
of renal failure (besides HT)of renal failure (besides HT)
Marker of Increased Risk for CV mortality Marker of Increased Risk for CV mortality and morbidity (DM & non-DM)and morbidity (DM & non-DM)
e.g. Microalbuminuria is associated with a 100- e.g. Microalbuminuria is associated with a 100- 150% increase in death rate150% increase in death rate
(Mogensen CE, New Eng. J. Med 1984;310:310-60)(Mogensen CE, New Eng. J. Med 1984;310:310-60)
Evaluation of Symptomatic HaematuriaEvaluation of Symptomatic Haematuria
Detection of Microscopic hematuria>5RBC/hpf or +ve dipstik test
Primary care investigationHistoryExaminationRenal functionUrine microscopy and culture
Consider Urological referral
Exclude benign causes :Menstruating womenWomen with UTIFalse +ve result Recent strenous exerciseSexual activity, viral illness,trauma etc
ProteinuriaRed cell cast/dysmorphic red blood cellsRenal Impairment
Nephrological referral
Isolated microscopis, hematuria and age > 40 yricroscopic haematuria and age >40 years
PathophysiologyPathophysiology Repeated injury Repeated injury to kidneyto kidney
SymptomsSymptoms HematuriaHematuria Flank painFlank pain EdemaEdema HypertensionHypertension Signs of uremiaSigns of uremia Lethargy and fatigueLethargy and fatigue Loss of appetiteLoss of appetite If asymptomatic may have elevated serum If asymptomatic may have elevated serum
creatinine concentration or an abnormal creatinine concentration or an abnormal urinalysisurinalysis
Risk FactorsRisk Factors Age of more than 60 yearsAge of more than 60 years Hypertension and Diabetes Hypertension and Diabetes
Responsible for 2/3 of casesResponsible for 2/3 of cases Cardiovascular disease Cardiovascular disease Family history of the disease. Family history of the disease. Race and ethnicityRace and ethnicity
Highest incidence is for African AmericansHighest incidence is for African Americans Hispanics have higher incidence rates of Hispanics have higher incidence rates of
ESRD than non-Hispanics.ESRD than non-Hispanics.
NKF-K/DOQI Stages of “CKD”NKF-K/DOQI Stages of “CKD”StageStage DescriptionDescription GFRGFR
(mL/min/(mL/min/1.73m2)1.73m2)
11 Kidney damage Kidney damage with normal or with normal or GFRGFR
> 90> 90
22 Mild Mild GFR GFR 60-8960-8933 Moderate Moderate GFR GFR 30-5930-5944 Severe Severe GFR GFR 15-2915-2955 Kidney FailureKidney Failure < 15 or < 15 or
dialysis dialysis
Primary CareFocus is here!
Prevalence of CKD by GFR in the Prevalence of CKD by GFR in the USAUSA
(There is a lot of CKD!)(There is a lot of CKD!)StageStage DescriptionDescription GFRGFR
(mL/min/(mL/min/1.73m2)1.73m2)
PrevalencPrevalencee
PrevalencPrevalence (%)e (%)
11 Kidney damage Kidney damage with normal or with normal or GFRGFR
> 90> 90 5.9 million5.9 million 3.3%3.3%
22 Mild Mild GFR GFR 60-8960-89 5.3 million5.3 million 3.0%3.0%33 Moderate Moderate GFR GFR 30-5930-59 7.6 million7.6 million 4.3%4.3%44 Severe Severe GFR GFR 15-2915-29 400,000400,000 0.2%0.2%55 Kidney FailureKidney Failure < 15 or dialysis < 15 or dialysis
300,000300,000 0.2%0.2%
Coresh, et al, Am J Kidney Dis. 2003; 41: 1-12
Causes of ESRD in the USA: Prevalent Counts and Adjusted
Rates by Primary Diagnosis
2006 ADR: USRDS
The Patient with early The Patient with early stage CKD is 5 to 10 times stage CKD is 5 to 10 times more likely to die from a more likely to die from a
cardiovascular event than cardiovascular event than progress to ESRD.progress to ESRD.
Foley RN, Murray AM, Li S, Herzog CA, McBean AM, Eggers Foley RN, Murray AM, Li S, Herzog CA, McBean AM, Eggers PW, Collins AJ. Chronic kidney disease and the risk for PW, Collins AJ. Chronic kidney disease and the risk for cardiovascular disease, renal replacement, and death in the cardiovascular disease, renal replacement, and death in the United States Medicare population, 1998 to 1999. J Am Soc United States Medicare population, 1998 to 1999. J Am Soc Nephrol 2005; 16:489-95.Nephrol 2005; 16:489-95.
So what do we do about So what do we do about this?this?
Chronic Kidney DiseaseChronic Kidney Disease In 1999, the NKF approved a proposal for In 1999, the NKF approved a proposal for
K/DOQI, Kidney Disease Outcomes Quality K/DOQI, Kidney Disease Outcomes Quality Initiative (an evolution of the DOQI (Dialysis Initiative (an evolution of the DOQI (Dialysis Outcomes Quality Initiative).Outcomes Quality Initiative).
The purpose was to develop clinical practice The purpose was to develop clinical practice guidelines for the spectrum of kidney diseases.guidelines for the spectrum of kidney diseases.
In February 2002, Clinical Practice Guidelines In February 2002, Clinical Practice Guidelines for Chronic Kidney Disease (CKD): Evaluation, for Chronic Kidney Disease (CKD): Evaluation, Classification, and Stratification were Classification, and Stratification were published.published.
Find the KDOQI guidelines atFind the KDOQI guidelines athttp://www.kidney.org/professionals/KDOQI/http://www.kidney.org/professionals/KDOQI/
Guideline 1. Definition and Guideline 1. Definition and Stages of Chronic Kidney Stages of Chronic Kidney
Disease Disease Adverse outcomes of CKD can often be prevented Adverse outcomes of CKD can often be prevented
or delayed through early detection and or delayed through early detection and treatment. Earlier stages of CKD can be detected treatment. Earlier stages of CKD can be detected through routine laboratory measurements. through routine laboratory measurements.
The presence of CKD should be established, The presence of CKD should be established, based on presence of kidney damage and level of based on presence of kidney damage and level of kidney function (glomerular filtration rate [GFR]), kidney function (glomerular filtration rate [GFR]), irrespective of diagnosis.irrespective of diagnosis.
Among patients with CKD, the stage of disease Among patients with CKD, the stage of disease should be assigned based on the level of kidney should be assigned based on the level of kidney function, irrespective of diagnosis, according to function, irrespective of diagnosis, according to the K/DOQI CKD classification the K/DOQI CKD classification
Who should we screen?
How should we screen?
Serum Creatinine, CrCl, and Serum Creatinine, CrCl, and eGFR--Nothing is Perfect!eGFR--Nothing is Perfect!
Serum Creatinine alone CAN NOT be used to Serum Creatinine alone CAN NOT be used to accurately assess level of kidney function.accurately assess level of kidney function.
SS. creatinine is a function of production (muscle . creatinine is a function of production (muscle mass) and excretion (both GFR and tubular mass) and excretion (both GFR and tubular secretion).secretion).
Age, sex, and lean body mass have to be taken Age, sex, and lean body mass have to be taken into account.into account.
Estimations of eGFR (MDRD equation) and CrCl Estimations of eGFR (MDRD equation) and CrCl (Cockcroft-Gault equation) were NOT developed in (Cockcroft-Gault equation) were NOT developed in subjects with normal renal function or normal subjects with normal renal function or normal health.health.
Increase Decrease
Factors Affecting Serum Factors Affecting Serum Creatinine ConcentrationCreatinine Concentration
Kidney Disease Kidney Disease KetoacidosisKetoacidosis Ingestion of cooked Ingestion of cooked
meat meat Drugs: Drugs:
TrimethoprimTrimethoprim CimetidineCimetidine FlucytosineFlucytosine Some cephalosporinsSome cephalosporins
Reduced Muscle Reduced Muscle Mass Mass
MalnutritionMalnutrition
Remember….GFR normally decreases with age!
Cockcroft-Gault Equation to Cockcroft-Gault Equation to Predict GFRPredict GFR
Developed to predict creatinine clearance, thus Developed to predict creatinine clearance, thus an overestimate of GFR an overestimate of GFR
Prediction based on age, gender, creatinine and Prediction based on age, gender, creatinine and ideal body weightideal body weight
ClClCrCr (cc/min) = [140-age] x IBW/72 x S (cc/min) = [140-age] x IBW/72 x SCrCr x [0.85 if x [0.85 if female] female]
Used almost universally as the basis for Used almost universally as the basis for drug dosing!drug dosing!
Get it athttp://www.kidney.org/professionals/KDOQI/gfr.cfm
MDRD Equation to Predict MDRD Equation to Predict GFRGFR
Prediction based on age, gender, race and Prediction based on age, gender, race and serum creatinine. Developed to follow serum creatinine. Developed to follow GFR as part of the Modification of Diet in GFR as part of the Modification of Diet in Renal Disease (MDRD) study. Validated.Renal Disease (MDRD) study. Validated.
GFR/1.73mGFR/1.73m22 = 186 x [P = 186 x [Pcrcr]]-1.154-1.154 x [age] x [age]-0.203-0.203 x x [0.742 if female] x [1.212 if AfAm] [0.742 if female] x [1.212 if AfAm]
TA-DA!TA-DA!(Your on-line link to the MDRD GFR (Your on-line link to the MDRD GFR
calculator)calculator)
http://www.kidney.org/professionals/KDOQI/gfr.cfm
Cockcroft-Gault vs. MDRDCockcroft-Gault vs. MDRD The MDRD equation estimates The MDRD equation estimates GFR.GFR.
eGFR is given per 1.73meGFR is given per 1.73m22 BSA BSA The Cockcroft-Gault equation The Cockcroft-Gault equation
estimates estimates CrCl.CrCl. CrCl is best used for drug dosing CrCl is best used for drug dosing
decisions--drug dosing is usually decisions--drug dosing is usually indexed to CrCl.indexed to CrCl.
Comparing the Cockcroft-Gault and MDRD:Do these patients have the same level of renal
function?• 20 year old AfAm Washington Redskins tackle, weighing 144 kg with a SCr 1.2 mg/dl?
ClCr=[140-20][144]/72 x [1.2] =200 cc/min
• 93 year old Caucasian female nursing home resident, weighing
44 kg with a SCr 1.2 mg/dl. ClCr = [140-93][44]/72 x [1.2] x 0.85 = 20 cc/min
MDRD GFR Value:99 mL/min/1.73 m2
MDRD GFR Value:45 mL/min/1.73 m2
YES NO
Risk Factor ReductionDetermine Stage of CKD Determine underlying cause Identify risk factors for progression Identify comorbidites
Patient meets definition of Chronic Kidney Disease?
Tools for Determining the Cause of Tools for Determining the Cause of Chronic Kidney DiseaseChronic Kidney Disease
CKD is often silent. Assessment relies CKD is often silent. Assessment relies on laboratory testing and imaging. on laboratory testing and imaging.
A Good History! ROS, existence of A Good History! ROS, existence of chronic diseases (DM, HTN, CHF, chronic diseases (DM, HTN, CHF, cirrhosis), medication review, accurate cirrhosis), medication review, accurate PMH and FH of kidney disease.PMH and FH of kidney disease.
Helpful Physical Examination! BP, Helpful Physical Examination! BP, evidence of co-morbid conditions and evidence of co-morbid conditions and complications of CKD. complications of CKD.
A Simple Laboratory Evaluation!
Simplified Classification of CKD Simplified Classification of CKD by Diagnosisby Diagnosis
Diabetic Kidney Diabetic Kidney Disease Disease
Nondiabetic Nondiabetic Kidney DiseaseKidney Disease Glomerular disease Glomerular disease
autoimmune, sytemic infections, autoimmune, sytemic infections, drugs, neoplasia, idiopathic drugs, neoplasia, idiopathic
Vascular disease Vascular disease ischemic renal disease, ischemic renal disease,
hypertensive nephrosclerosis, hypertensive nephrosclerosis, microangiopathy microangiopathy
Tubulointerstitial disease Tubulointerstitial disease UTO, stones, UTI, drug toxicity UTO, stones, UTI, drug toxicity
Cystic diseaseCystic disease Post-TransplantPost-Transplant
Differential Diagnosis of Chronic Differential Diagnosis of Chronic Kidney DiseaseKidney Disease
Everyone deserves a diagnosis!Everyone deserves a diagnosis! This is especially true for Stage 1 or 2 This is especially true for Stage 1 or 2
CKD!CKD! When in doubt, consult a nephrologist!When in doubt, consult a nephrologist! Initial evaluation will guide further Initial evaluation will guide further
diagnostics, decisions about renal biopsy diagnostics, decisions about renal biopsy and often decisions about treatment and and often decisions about treatment and prognosis. prognosis.
So Now What Do You Do? (There’s a lot you can do!)
CKD Clinical Action Plan On-LineCKD Clinical Action Plan On-Line
http://www.kidney.org/professionals/kdoqi/cap/index.html
Primary Goals of CKD Primary Goals of CKD CareCare
• To prevent cardiovascular events and deathTo prevent cardiovascular events and death• Heart AttacksHeart Attacks• Congestive Heart FailureCongestive Heart Failure• Sudden Cardiac DeathSudden Cardiac Death• StrokeStroke
• To prevent the progression of CKD to Kidney To prevent the progression of CKD to Kidney Failure or ESRDFailure or ESRD
• To prevent complications of CKDTo prevent complications of CKD• To prepare for dialysis/transplantation in a To prepare for dialysis/transplantation in a
timely mannertimely manner
Clinical Action PlanClinical Action Plan• A Clinical Action Plan should be developed for each A Clinical Action Plan should be developed for each
patient, based on the stage of CKD (see patient, based on the stage of CKD (see Table 33).Table 33). Patients with CKD should be evaluated to determine:Patients with CKD should be evaluated to determine:
DiagnosisDiagnosis Comorbid ConditionsComorbid Conditions Severity, assessed by level of kidney functionSeverity, assessed by level of kidney function Complications, related to level of kidney functionComplications, related to level of kidney function Risk for loss of kidney functionRisk for loss of kidney function Risk for cardiovascular diseaseRisk for cardiovascular disease
• Review of medications should be performed at all visits.Review of medications should be performed at all visits.• Self-management behaviors should be incorporated into Self-management behaviors should be incorporated into
the treatment plan at all stages of chronic kidney disease.the treatment plan at all stages of chronic kidney disease.
Management of Patients with Management of Patients with Chronic Kidney DiseaseChronic Kidney Disease
B lood g lu cose con tro l
B P C on tro l
A R B s
A C E In h ib itors
In te rven tion s th a t d e lay p rog res s ion
R ed u ced F u n c tion in g an d W ell-b e in g
M aln u trit ion
O s teod ys trop h y
A n em ia
P reven tion o f U rem ic C om p lic a t ion s(G F R < 6 0 c c /m in /1 .7 3 m 2 )
C ard iovascu la r D is ease
M od ifca tion of C om orb id ity
P re -em p tive Tran sp lan tat ion
K id n ey Tran sp lan t E valu a tion
Tim e ly D ia lys is In it ia t ion
Tim ely D ia lys is A cces s P lacem en t
C h o ice o f D ia lys is M od a lity
E d u cationA n "E S R D C lin ic "
P rep arat ion for R en a l R ep lacem en t Th e rap y(G R F < 3 0 cc /m in /1 .7 3 m 2 )
E arly D etec tion o f C K D
RENAL INJURY
Reduction in nephron mass
Glomerular capillary hypertension
Increased glomerular permeability
to macromolecules
Increased filtration of plasma proteinsProteinuria
Excessive tubular protein reabsorption
Tubulointerstitial inflammation
RENAL SCARRING
PROGRESSIVE RENAL DAMAGE:
The Final Common Pathway
Increased BP
Nonmodifiable Modifiable
Patient characteristics Patient characteristics associated with increased rate associated with increased rate
of GFR declineof GFR decline African American African American
race race Male gender Male gender Older ageOlder age Lower baseline Lower baseline
level of kidney level of kidney function function
Higher level of Higher level of proteinuria proteinuria
Higher BP Higher BP Poor glycemic Poor glycemic
control control SmokingSmoking
GUIDELINE 13. LOSS OF KIDNEY FUNCTION IN CKD Interventions to slow the progression should be considered in all patients with CKD
Interventions proven to be effective include: 1. Strict glucose control in diabetes; 2. Strict blood pressure control; 3. ACEI and ARBs
Interventions that may be effective, but studies are inconclusive, include: 1. Dietary protein restriction; 2. Lipid-lowering therapy; 3. Partial correction of anemia.
Attempts should be made to prevent acute renal failure: •Volume depletion; •IV contrast; •Some antibiotics (for example, aminoglycosides and amphotericin B); •NSAIDs, including COX 2 inhibitors; •Other drugs: ACEI, ARBs, calcineurin inhibitors •Obstruction.
eGFR should be obtained at least yearly in CKD, and more often in patients with: •GFR <60 mL/min/1.73 m2; •Fast GFR decline in the past •Risk factors for faster progression; •Ongoing treatment to slow progression; •Exposure to risk factors for acute GFR decline.
Slowing ProgressionThe Earlier, the Better…
Interventions that delay progression Interventions that delay progression of CKD: ACEI and ARBsof CKD: ACEI and ARBs
Mechanisms Mechanisms Lower systemic blood pressure Lower systemic blood pressure Lower glomerular capillary blood pressure Lower glomerular capillary blood pressure
and protein filtrationand protein filtration Reduce AT II mediated cell proliferation and Reduce AT II mediated cell proliferation and
fibrosisfibrosis
Should be employed in all proteinuric kidney diseases!
Measuring Proteinuria—Get into the right spot!
When you get to this point,Don’t continue to get microalbumin!
RENAL INJURY
Reduction in nephron mass
Glomerular capillary hypertension
Increased glomerular permeability
to macromolecules
Increased filtration of plasma proteinsProteinuria
Excessive tubular protein reabsorption
Tubulointerstitial inflammation
RENAL SCARRING
PROGRESSIVE RENAL DAMAGE:
The Final Common Pathway
Increased BP ACEI ARB
ACEI ARB
ACEI ARB
Interventions that delay Interventions that delay progression of CKD: ACEI and progression of CKD: ACEI and
ARBsARBs Diabetic Kidney Disease Diabetic Kidney Disease
ACEI or ARB in all diabetic patients with microalbuminuriaACEI or ARB in all diabetic patients with microalbuminuria ACEI (alt ARB) for Type 1 Diabetics with macroalbuminuriaACEI (alt ARB) for Type 1 Diabetics with macroalbuminuria ARB (alt. ACEI) in Type 2 Diabetics with macroalbuminuriaARB (alt. ACEI) in Type 2 Diabetics with macroalbuminuria
Nondiabetic Kidney Disease Nondiabetic Kidney Disease ACEI/ARB recommended in all proteinuric (>200 mg/g Cr ACEI/ARB recommended in all proteinuric (>200 mg/g Cr
on spot urine) patients with CKDon spot urine) patients with CKD May tolerate creatinine rise of 35% above baselineMay tolerate creatinine rise of 35% above baseline <130/80 is goal<130/80 is goal 3 or more drugs may be required! One will probably be a 3 or more drugs may be required! One will probably be a
diuretic (thiazide first, then loop)diuretic (thiazide first, then loop) ACEI and ARB may be used in combinationACEI and ARB may be used in combination
-KDOQI Guideline 8, Table 110-JNC 7, 2003 http://www.nhlbi.nih.gov/guidelines/hypertension/express.pdf
-HTN is both a cause and a complication of CKD. -HTN may develop early during the course of CKD and is associated with adverse outcomes—in particular, faster loss of kidney function and development of CVD. -Blood pressure should be closely monitored in all patients with chronic kidney disease.-Treatment of high blood pressure in CKD should include specification of target BP levels, nonpharmacologic therapy, and specific antihypertensive agents for the prevention of progression of kidney disease and development of cardiovascular disease.
Controlling HypertensionControlling HypertensionGUIDELINE 7. ASSOCIATION OF LEVEL OF GFR GUIDELINE 7. ASSOCIATION OF LEVEL OF GFR
WITH HYPERTENSIONWITH HYPERTENSION
Pathogenic Mechanisms of High Pathogenic Mechanisms of High Blood Pressure in CKDBlood Pressure in CKD
Pre-existing essential hypertension Pre-existing essential hypertension Extracellular fluid volume expansion Extracellular fluid volume expansion Renin-agniotensin aldosterone system stimulation Renin-agniotensin aldosterone system stimulation Increased sympathetic activity Increased sympathetic activity Alteration in endothelium-derived Alteration in endothelium-derived
factors(NO/endothelin) factors(NO/endothelin) Increased body weight Increased body weight Erythropoietin administration Erythropoietin administration PTH secretion/hypercalcemia PTH secretion/hypercalcemia calcified arterial tree calcified arterial tree renal vascular disease and renal artery stenosis renal vascular disease and renal artery stenosis
Relationship between BP and progression of diabetic nephropathy. BP, albumin excretion rate, and GFR in patients with type 1 DMs randomly assigned to a reduction in MAP of 10 mm Hg using metoprolol at 100 to 400 mg/d, hydralazine at 50 to 200 mg/d, and furosemide at 80 to 500 mg/d versus no antihypertensive therapy. Solid circles represent the treated group. Open circles represent the control group. Vertical lines represent standard error. Study was stopped earlier in the control group because of faster decline in GFR. Reprinted with permission.253
BP vs. Time
Controls
AER vs. Time GFR vs. Time
Controls
Controls
Controls
Relationship between MAP and GFR decline (Non-diabetic Pts). Mean GFR decline and achieved follow-up BP in MDRD Study A (patients with baseline GFR 25 to 55 mL/min/1.73 m2). Regression lines relating the estimated mean GFR decline over 3 years to mean follow-up MAP for groups of patients defined according to baseline proteinuria. Within each group, a 3-slope model was used with break points at 92 and 98 mm Hg. Reprinted with permission.255
“Nephrotic”
JNC-7 recommends a goal blood pressure of <130/80 mm Hg for individuals with high blood
pressure and CKD. http://www.nhlbi.nih.gov/guidelines/hypertension/express.pdf
Population BP Goal Nondrug Rx Drug RX
CKD + >200mg/g <130/80 Reduce salt ACEI/ARBProt/Cr Ratio BMI≤25 kg/m2 Then diuretic
Mod EtOH Then BB or CCBStop SmokingExercise
CKD + no proteinuria <130/80 Same Thiazide/LoopThen ACEI/ARBThen BB or CCB
Recommendations for Controlling HTN in Non-Diabetic CKD
KDOQI Table 118, Guideline 9
Interventions that delay Interventions that delay progression of CKD: Strict progression of CKD: Strict
Glycemic ControlGlycemic Control 80% Type I DM with microalbuminuria 80% Type I DM with microalbuminuria
develop DN in 10-15years, 50% to ESRD develop DN in 10-15years, 50% to ESRD DCCT, benefit of tight control in reducing DCCT, benefit of tight control in reducing
occurrence subclinical and overt DN(40-60%) occurrence subclinical and overt DN(40-60%) 20-40% Type II DM with microalbuminuria 20-40% Type II DM with microalbuminuria
develop DN, 20% to ESRD develop DN, 20% to ESRD UKPDS 33, 25% reduction in UKPDS 33, 25% reduction in microvascular microvascular
eventsevents Kumamoto Kumamoto Steno Type 2, 73% reduction in clinical Steno Type 2, 73% reduction in clinical
proteinuriaproteinuria
Interventions that delay Interventions that delay progression of CKD: Strict progression of CKD: Strict
Glycemic ControlGlycemic ControlRecommended Therapy: Recommended Therapy: HgbAHgbA1c1c < 7% < 7% Additional information in 2001 ADA Additional information in 2001 ADA
Clinical Practice Guidelines Clinical Practice Guidelines www.diabetes.org/clinicalrecommendations/www.diabetes.org/clinicalrecommendations/
Supplement101/S3.htmSupplement101/S3.htm
Management of Patients with Management of Patients with Chronic Kidney DiseaseChronic Kidney Disease
B lood g lu cos e con tro l
B P C on tro l
A R B s
A C E In h ib ito rs
In te rven tion s th a t d e lay p rog ress ion
R ed u c ed F u n c tion in g an d W ell-b e in g
M a ln u trit ion
O s teod ys trop h y
A n em ia
P reven tion o f U rem ic C om p lica tion s(G F R < 6 0 cc /m in /1 .7 3 m 2 )
C ard iovas cu la r D is ease
M od ifca tion o f C om orb id ity
P re -em p tive Tran sp lan ta t ion
K id n ey Tran sp lan t E valu a tion
Tim e ly D ia lys is In it ia t ion
Tim ely D ia lys is A ccess P lac em en t
C h o ic e o f D ia lys is M od a lity
E d u cationA n "E S R D C lin ic "
P rep ara tion for R en a l R ep lacem en t Th e rap y(G R F < 3 0 cc /m in /1 .7 3 m 2 )
E arly D etec tion o f C K D
When to Expect Complications…
Anemia and CKDAnemia and CKD• Anemia usually develops during the course of chronic Anemia usually develops during the course of chronic
kidney disease and may be associated with adverse kidney disease and may be associated with adverse outcomes. outcomes.
• Anemia is one of the modifiable complications of CKDAnemia is one of the modifiable complications of CKD ..• All individuals with hemoglobin (Hb) levels lower than All individuals with hemoglobin (Hb) levels lower than
physiologic norms are considered anemic.physiologic norms are considered anemic. Erythropoietin deficiency is the primary cause of anemia of Erythropoietin deficiency is the primary cause of anemia of
CKD.CKD. The NKF recommends that evaluation for anemia should occur The NKF recommends that evaluation for anemia should occur
when GFR <60 mL/min/1.73 mwhen GFR <60 mL/min/1.73 m22; measurement should include ; measurement should include Hb level.Hb level.
Anemia should be treated according to the K/DOQIAnemia should be treated according to the K/DOQITMTM guidelines guidelines for anemia of CKD.for anemia of CKD.
K/DOQI: K/DOQI: Evaluation and Management Evaluation and Management of Anemiaof Anemia
For Adults with ≥ Stage 3 CKD:For Adults with ≥ Stage 3 CKD: Assess Hemoglobin level Assess Hemoglobin level If anemia (HgB ≤ 12) If anemia (HgB ≤ 12)
RBC indices/CBCRBC indices/CBC Reticulocyte countReticulocyte count Iron studiesIron studies Test for occult GI bleeding as indicatedTest for occult GI bleeding as indicated Medical evaluation of comorbid conditionsMedical evaluation of comorbid conditions
Erythropoetin levels are usually NOT Erythropoetin levels are usually NOT indicated.indicated.
Prevention of Uremic Prevention of Uremic Complications:Complications:
Anemia TherapyAnemia Therapy Subcutaneous administration of Subcutaneous administration of
erythropoietin once to thrice weekly erythropoietin once to thrice weekly (sometimes less).(sometimes less).
Supplemental oral or IV iron to keep Supplemental oral or IV iron to keep ferritin > 100 and iron saturation >20%.ferritin > 100 and iron saturation >20%.
Monthly monitoring of Hgb, iron stores.Monthly monitoring of Hgb, iron stores. Monthly adjustments in EPO dose and Monthly adjustments in EPO dose and
frequency to meet target Hgb 11-12 frequency to meet target Hgb 11-12 g/dl (HCT 33-36%).g/dl (HCT 33-36%).
•Bone disease and disorders of calcium and phosphorus metabolism develop during the course of chronic kidney disease and are associated with adverse outcomes.
-Patients with GFR <60 mL/min/1.73 m2 should be evaluated for bone disease and disorders of calcium and phosphorus metabolism.-Patients with bone disease and disorders of bone metabolism should be evaluated and treated—see K/DOQI Clinical Practice Guidelines on Bone Metabolism and Disease in Chronic Kidney Disease (October, 2004).
GUIDELINE 10. ASSOCIATION OF LEVEL OF GFR WITH BONE DISEASE AND DISORDERS OF CALCIUM AND
PHOSPHORUS METABOLISM
Prevention of Uremic Prevention of Uremic Complications:Complications:OsteodystrophyOsteodystrophy
Osteitis fibrosis cystica, due to 2Osteitis fibrosis cystica, due to 2o o HPT, is HPT, is major form of bone disease.major form of bone disease.
Check indices of bone and mineral Check indices of bone and mineral metabolism at GFR < 60 cc/min/1.73mmetabolism at GFR < 60 cc/min/1.73m2:2:
iPTH the earliest markeriPTH the earliest marker Hypocalcemia, hyperphosphatemia Hypocalcemia, hyperphosphatemia Phosphorus control is cornerstone of Phosphorus control is cornerstone of
treatment treatment
Prevention of Uremic Prevention of Uremic Complications:Complications:
Osteodystrophy TherapyOsteodystrophy Therapy Restrict dietary phosphorus to 800-Restrict dietary phosphorus to 800-
1,000 mg/d 1,000 mg/d Calcium-based phosphate binders Calcium-based phosphate binders
(but not with Vit D!) to combat (but not with Vit D!) to combat hypocalcemia and bind phosphorus hypocalcemia and bind phosphorus
Assure repletion of Vitamin D 25 Assure repletion of Vitamin D 25 Avoid acidosis, HCOAvoid acidosis, HCO33> 23 mEq/l> 23 mEq/l
Management Management of Renal of Renal
OsteodystropOsteodystrophy is Very hy is Very Complex!Complex!
http://www.kidney.org/professionals/KDOQI/
guidelines_bone/index.htm
•Protein energy malnutrition develops during the course of chronic kidney disease and is associated with adverse outcomes. Low protein and calorie intake is an important cause of malnutrition in chronic kidney disease.
•Patients with GFR <60 mL/min/1.73 m2 should undergo assessment of dietary protein and energy intake and nutritional status:
•Guideline 23. Panels of Nutritional Measures for Nondialyzed Patients: "For individuals with CRF (GFR <20 mL/min) protein-energy nutritional status should be evaluated by serial measurements of a panel of markers including at least one value from each of the following clusters:
(1) Serum albumin; (2) Edema-free actual body weight, percent standard (NHANES II) body weight, or subjective global assessment (SGA); and (3) Normalized protein nitrogen appearance (nPNA) or dietary interviews and diaries. (Evidence and Opinion)"
•Guideline 26. Intensive Nutritional Counseling for Chronic Renal Failure: "The nutritional status of individuals with CRF should be monitored at regular intervals."
GUIDELINE 9. ASSOCIATION OF LEVEL OF GFR WITH NUTRITIONAL STATUS
Prevention of Uremic Prevention of Uremic Complications:Complications:
MalnutritionMalnutrition Contributors to protein-energy Contributors to protein-energy
malnutrition(PEM) in CKD: malnutrition(PEM) in CKD: low protein and calorie intake low protein and calorie intake metabolic acidosis metabolic acidosis resistance to insulin, GH, IGF-1 resistance to insulin, GH, IGF-1 proinflammatory cytokines proinflammatory cytokines
Assessment of nutritional status requires Assessment of nutritional status requires multiple markers to assess protein multiple markers to assess protein status, fat stores, body composition and status, fat stores, body composition and dietary protein and energy intake. dietary protein and energy intake.
Prevention of Uremic Prevention of Uremic Complications:Complications:
Nutrition GuidelinesNutrition Guidelines Protein intake Protein intake
0.75g/kg/d (RDA) 0.75g/kg/d (RDA) GFR < 25 cc/min(Stages 4-5) consider 0.6g/kg/d GFR < 25 cc/min(Stages 4-5) consider 0.6g/kg/d
Energy intake Energy intake RDA depends on energy expenditure RDA depends on energy expenditure GFR < 25 cc/min(Stages 4-5) 30-35kcal/kg/d GFR < 25 cc/min(Stages 4-5) 30-35kcal/kg/d
Patients with less than recommended Patients with less than recommended intake need frequent follow-up of nutritional intake need frequent follow-up of nutritional statusstatus
Prevention of Uremic Prevention of Uremic Complications:Complications:
Just a Word About Just a Word About ImmunizationsImmunizations Don’t forget to continue routine immunizations, Don’t forget to continue routine immunizations,
e.g.e.g. TetanusTetanus PneumococcusPneumococcus Influenza Influenza
Hepatitis B Hepatitis B Check for immunity first--ie, hepatitis B sAb, sAg, cAb Check for immunity first--ie, hepatitis B sAb, sAg, cAb Those who are immune or have chronic infection do not Those who are immune or have chronic infection do not
need the vaccine.need the vaccine. All others should receive the vaccine. Don’t wait for All others should receive the vaccine. Don’t wait for
dialysis! Patients with advanced chronic kidney disease dialysis! Patients with advanced chronic kidney disease are less likely to gain immunity from the vaccine. are less likely to gain immunity from the vaccine. Consider for all Stage 3 or greater CKD patients!Consider for all Stage 3 or greater CKD patients!
Management of Patients with Management of Patients with Chronic Kidney DiseaseChronic Kidney Disease
B lood g lu c os e con tro l
B P C on tro l
A R B s
A C E In h ib ito rs
In te rven tion s th a t d e lay p rog ress ion
R ed u c ed F u n c tion in g an d W ell-b e in g
M a ln u trit ion
O s teod ys trop h y
A n em ia
P reven tion o f U rem ic C om p lica tion s(G F R < 6 0 c c /m in /1 .7 3 m 2 )
C ard iovas cu la r D is eas e
M od ifc a t ion of C om orb id ity
P re -em p tive Tran sp lan tat ion
K id n ey Tran sp lan t E va lu a tion
Tim e ly D ia lys is In it ia t ion
Tim ely D ia lys is A c ces s P lac em en t
C h o ic e o f D ia lys is M od a lity
E d u c ationA n "E S R D C lin ic "
P rep arat ion for R en a l R ep lacem en t Th erap y(G R F < 3 0 cc /m in /1 .7 3 m 2 )
E arly D etec tion o f C K D
Patients with CKD, irrespective of diagnosis, are at increased risk of cardiovascular disease (CVD), including coronary heart disease, cerebrovascular disease, peripheral vascular disease, and heart failure. Both “traditional” and “chronic kidney disease related (nontraditional)” CVD risk factors may contribute to this increased risk.
-All patients with CKD should be considered in the “highest risk” group for CVD, irrespective of levels of traditional CVD risk factors.-All patients with CKD should undergo assessment of CVD risk factors, including:
•Measurement of “traditional” CVD risk factors in all patients; •Individual decision-making regarding measurement of selected “CKD-related” CVD risk factors in some patients.
-Recommendations for CVD risk factor reduction should take into account the “highest-risk” status of patients with chronic kidney disease.
GUIDELINE 15. ASSOCIATION OF CHRONIC KIDNEY DISEASE WITH CARDIOVASCULAR DISEASE
The most common cause of death The most common cause of death among ESRD patients is CVDamong ESRD patients is CVD
Fig 5. Causes of death among period prevalent patients 1997–1999, treated with hemodialysis, peritoneal dialysis, or kidney transplantation. Data are from
the USRDS 2001 Annual Data Report (www.usrds.org). Abbreviations: MI, myocardial infarction; HD, heart disease.
Modification of Comorbidity:Modification of Comorbidity:Cardiovascular DiseaseCardiovascular Disease
CVD is the cause of death in 40-50% CVD is the cause of death in 40-50% ESRD patients ESRD patients
ESRD CVD mortality rates 15x higher ESRD CVD mortality rates 15x higher than general population. than general population.
CVD is leading cause of death in CVD is leading cause of death in patients with CKD, regardless of stage. patients with CKD, regardless of stage. HDFP, pts with CrHDFP, pts with Cr>> 1.7mg/dl, 58% deaths 1.7mg/dl, 58% deaths
CV CV British Regional Heart Study, 50% deaths British Regional Heart Study, 50% deaths
CV in patients in upper decile of baseline CrCV in patients in upper decile of baseline Cr
GFR and relative risk for CVD-related death. Wannamethee625: risk is for SCr 1.5 mg% vs SCr 1.3 mg%. Culleton622: risk is for SCr 1.5 mg% and 1.4 mg% vs. <1.5 and <1.4 in men and women respectively. Upper limit for SCr was 3.0 mg%. Mann637: risk is for SC 1.4 mg% vs <1.4 mg%. Ruilope634: risk is for SCr >1.5 mg% vs 1.5 mg%. Upper limit for SCr was 3.0 mg%. Fried640: risk is for SCr 1.5 mg% versus SCr 0.9 mg%. Hemmelgarn642: risk is for SCr >2.3 mg/dL vs
2.3 mg/dL.
Proteinuria and relative risk for cardiovascular disease. Where possible, results presented are from multivariable analyses. Agewall650, Ljungman647: Unadjusted results shown. Data not available to calculate age or multivariable adjusted risk.
Modification of Comorbidity:Modification of Comorbidity:Cardiovascular DiseaseCardiovascular Disease
Patients with CKD should be considered Patients with CKD should be considered highest riskhighest risk for CVD. for CVD.
Aggressive intervention and management Aggressive intervention and management of traditional CV risk factors is indicated.of traditional CV risk factors is indicated.
This particularly includes dyslipidemias.This particularly includes dyslipidemias. All adults with Stage1-5 CKD should be All adults with Stage1-5 CKD should be
evaluated for dyslipidemia.evaluated for dyslipidemia. Fasting lipid profile with total cholesterol, LDL, Fasting lipid profile with total cholesterol, LDL,
HDL and triglycerides, at baseline, and at HDL and triglycerides, at baseline, and at least annually.least annually.
Management of Dyslipidemia in Management of Dyslipidemia in CKDCKD
Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA, 2001, 285;2486-2497.
http://www.kidney.org/professionals/KDOQI/guidelines_lipids/index.htm
Management of Patients with Management of Patients with Chronic Kidney DiseaseChronic Kidney Disease
B lood g lu cos e con tro l
B P C on tro l
A R B s
A C E In h ib ito rs
In te rven t ion s th a t d elay p rog ress ion
R ed u c ed F u n c tion in g an d W e ll-b e in g
M a ln u trit ion
O s teod ys trop h y
A n em ia
P re ven tion o f U rem ic C om p lic a tion s(G F R < 6 0 cc /m in /1 .7 3 m 2 )
C ard iovas cu la r D isease
M od ifc a tion o f C om orb id ity
P re -em p tive Tran sp lan ta tion
K id n ey Tran sp lan t E va lu a t ion
Tim e ly D ia lys is In it ia tion
Tim e ly D ia lys is A c cess P la cem en t
C h o ice o f D ia lys is M od a lity
E d u ca t ionA n "E S R D C lin ic "
P rep ara tion fo r R en al R ep lacem en t Th erap y(G R F < 3 0 cc /m in /1 .7 3 m 2 )
E arly D etec t ion o f C K D
When to Refer!When to Refer! Consider co-management with a nephrologist if Consider co-management with a nephrologist if
the clinical action plan cannot be carried out.the clinical action plan cannot be carried out. Consider subspecialty referral when*: Consider subspecialty referral when*:
Unexplained proteinuria (>1gm/day) or Unexplained proteinuria (>1gm/day) or microalbumin/Cr ratio >250mg albumin/gCrmicroalbumin/Cr ratio >250mg albumin/gCr
Unexplained macroscopic or microscopic hematuriaUnexplained macroscopic or microscopic hematuria Diabetes and macroalbuminuriaDiabetes and macroalbuminuria Multiple and recurring kidney stonesMultiple and recurring kidney stones Rapidly deteriorating kidney functionRapidly deteriorating kidney function Difficult to control hypertensionDifficult to control hypertension
Refer to a nephrologist when Refer to a nephrologist when GFR <30 GFR <30 mL/min/1.73 mmL/min/1.73 m22 (CKD Stages 4-5)! (CKD Stages 4-5)!
Mandatory Referral to Nephrologist guideline, Niagara Health Quality Coalition, NY
Fig 11. Level of GFR at initiation of replacement therapy (USRDS). Data from Obrador et al.77
DiabeticsMedicare EligibleMost should have started
Preparation for Renal Preparation for Renal Replacement TherapyReplacement Therapy
(GFR < 30cc/min/1.73m(GFR < 30cc/min/1.73m22)) Referral to a Nephrologist allows: Referral to a Nephrologist allows:
Early identification of RRT modality. Early identification of RRT modality. Evaluation for kidney transplantation with Evaluation for kidney transplantation with
goal of pre-emptive transplantation. goal of pre-emptive transplantation. REMEMBER, in eligible patients REMEMBER, in eligible patients
transplantation confers a survival transplantation confers a survival advantage over dialysis!advantage over dialysis!
Identification of social, functional or Identification of social, functional or nutritional needs.nutritional needs.
Preparation for Renal Preparation for Renal Replacement TherapyReplacement Therapy
(GFR < 30cc/min/1.73m(GFR < 30cc/min/1.73m22)) Close coordination between PCM Close coordination between PCM
and nephrologist allows:and nephrologist allows: Timely placement of dialysis accessTimely placement of dialysis access Timely initiation of dialysisTimely initiation of dialysis Timely referral for transplant Timely referral for transplant
evaluation with preemptive transplant evaluation with preemptive transplant if possible.if possible.
ConclusionsConclusions CKD is a public health problem with poor CKD is a public health problem with poor
outcomes and high cost. CKD is outcomes and high cost. CKD is underdiagnosed underdiagnosed and and undertreatedundertreated in the in the U.S. U.S.
Early CKD detection and intervention Early CKD detection and intervention may increase opportunities for the may increase opportunities for the prevention of ESRD and of complications prevention of ESRD and of complications of CKD, including death. of CKD, including death.
YOU, the PCM, CAN MAKE A Difference!YOU, the PCM, CAN MAKE A Difference!