Updates in Chronic Kidney Disease (CKD)
Texas Academy of Family Physicians 4/4/18
Michael J Choi, MDJohns Hopkins University School of Medicine
Speaker Disclosure
• Dr. Choi has disclosed the he is on the speaker’s bureau for AstraZeneca.
Learning Objectives
By completing this educational activity, the participant should be better able to:1. Risk stratify CKD patients by estimated GFR and albuminuria.2. Implement measures to slow CKD progression and manage CKD
complications including hypertension, metabolic acidosis, anemia, hyperkalemia, mineral and bone disorder, and medication safety.
3. Apply indications for nephrology referral to the context of practice.
CKD: A Public Health Issue
• 26 million American adults affected, 11‐13% of adults• Medicare cost $99 billion in 2015• Increases risk for all‐cause mortality, CV mortality, and ESRD• 6 fold increase in mortality rate with DM + CKD• Disproportionately affects African Americans, Hispanics, Asians, American Indians
1. NKF Fact Sheets. http://www.kidney.org/news/newsroom/factsheets/FastFacts. 2. USRDS. www.usrds.org. Accessed Nov 5, 2014.3. Coresh et al. JAMA. 2007. 298:2038‐2047.
CKD Stages – Old WayStage Description
GFRmL/min/1.73 m2
Prevalence(×1000)
1 Kidney damage with normal GFR ≥90 5900
2 Kidney damage with mildly decreased GFR 60‐89 5300
3 Moderately
decreased GFR30‐59 7600
4 Severely decreased GFR 15‐29 400
5 Kidney failure <15 or on dialysis 300
Adapted from: Coresh J, et al. Am J Kidney Dis. 2003;41:1‐12.
Focus: Primary Care Providers>3000 CKD patients per nephrologist
Who is at risk for CKD?
Clinical Factors Diabetes Hypertension Cardiovascular disease History of AKI Family history of CKD/ESRD
Sociodemographic Factors Age > 60 years US ethnic minority:
‐ African American‐ Hispanic‐ Asian or Pacific Islander‐ American Indian
Why do we stink at diagnosing CKD?
Cr based on muscle mass
Non‐linear relationship ‐ Insensitive
Determining GFR• Serum creatinine is a POOR measure of kidney function ‐especially in older women
• CKD‐EPI equation (estimated GFR mL/min/1.73m2)– Adjusts for demographics
Levey AS et al. Ann Intern Med. 2009;150:604‐612
SCr (mg/dl)
1.3
1.3
Age Gender RaceeGFR
(mL/min/1.73m2)
20 M B 91
70 F W 42
Screening Tools for CKD: ACR
• Urinary albumin‐to‐creatinine ratio (ACR) – urine albumin concentration in mg/dl divided by urine creatinine concentration in g/dl– Urine creatinine assists in adjusting for urine concentrations
• Categories of ACR (mg/g)– Mild (< 30 mg/g)– Moderate (30‐299 mg/g)– Severe (> 300 mg/g)
• 24hr urine test rarely necessary
Criteria for CKD
• One or more must be present for >3 months:–ACR >30 mg/g–Abnormalities of kidney structure or function, present for >3 months (albuminuria/proteinuria, hematuria, cysts)
–GFR <60 mL/min/1.73 m2
12
Albuminuria/Proteinuria and ESRD Risk
.51
416
6425
6102
481
92A
djus
ted
HR
15 30 45 60 75 90 105 120eGFR, ml/min/1.73m^2
End Stage Renal Disease
Gansevoort RT et al. Kidney Int 2011 epub Feb 2
>30030‐299 <30
Urine Albumin/Cr UACR (mg/g Cr)
Classify CKD Based on GFR and ACR – New Way
Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. Kidney Int Suppls. 2013;3:1‐150.
Risk Assessment: CKD & CVD Risk
Go AS, et al: NEJM. 2004: 351;1296‐1305
Age-Standardized Rates of Cardiovascular Events
2.11 3.65
11.29
21.8
36.6
05
10152025303540
>=60 45-49 30-44 15-29 <15
Estimated GFR (mL/min/1.73 m2)
Age-
Stan
dard
ized
Rat
e of
Ca
rdio
vasc
ular
Eve
nts
(per
10
0 pe
rson
-yr)
Age-Standardized Rates of Death from Any Cause According to GFR
0.76 1.08
4.76
11.36
14.14
02468
10121416
>=60 45-49 30-44 15-29 <15
Estimated GFR (mL/min/1.73m2)
Age-
Stan
dard
ized
Rat
e of
Dea
th fr
om A
ny
Caus
e (p
er 1
00 p
erso
n-yr
)
Kaiser N=1,120,295
CV Mortality with Risk Factors including eGFR and ACR
Matsushita et al. Lancet Diabetes Endocrinol 2015
‐0.04 ‐0.02 0.0
CKD AssessmentTwo, Widely Available, Inexpensive Tests for Diagnosis and Risk Stratification
• Kidney Profile- Combines eGFR & ACR- Test the Population at Risk with DM and/or HTN
- NKF Partnership with leading Clinical Laboratories nationwide
• Kidney Function- Estimated GFR (ml/min/1.73m2)
• Kidney Damage- Albumin‐creatinine ratio, urine (mg/g)
• Depending on age, history and physical– Serum light chain assay, serum or urine protein electrophoresis (SPEP, UPEP)
–HIV, HCV, HBV tests–Complements, other serologies – limited role unless specific reason
Clinical Evaluation of CKD
18
CKD or AKI from Obstruction
• Voiding symptoms– Diabetics, older men, – Anticholinergics, opiates
• Partial – Urine output variable • Dx: Ultrasound
– Kidney sizes normally 10‐12 cm – < 10 cm implies CKD
• Rx: Foley/nephrostomy tube
CKD Complications Start in Stage 3 and Progress
Mineral Bone Disorder
AnemiaAcidosis
Hypertension
Slow CKD Progression
Hyperkalemia
Reduce CV Disease
CKD
Acute Kidney InjuryMedication Safety
Diabetes Care 2017;40 (Suppl 1):S64‐74
SGLT2 Inhibitors – Proximal Tubule
21 J Clin Endocrinol Metab 2010
↓TGFβ↓inflammatory and fibro c markers
The primary composite outcome in the time‐to‐event analysis was the first occurrence of death from cardiovascular causes, non‐fatal myocardial infarction, or non‐fatal stroke. The cumulative incidences were estimated with the use of the Kaplan–Meier method, and the HRs with the use of the Cox proportional‐hazard regression model. The data analyses are truncated at 54 months because less than 10% of the patients had an observation time beyond 54 months. CI: confidence interval; CV: cardiovascular; HR: hazard ratio. Marso S et al. New Engl J Med 2016;375:311–322.
All cause death HR: 0.85
95% CI (0.74 ; 0.97)p=0.02
Primary OutcomeTime to CV death, non‐fatal myocardial infarction, or non‐fatal stroke
(N events= 1302)
Marso S et al. New Engl J Med 2016;375:311–322.
Empagliflozin and Incident/Worsening Nephropathy
23Wanner et al. N Engl J Med 2016;375:323‐34
• Type 2 diabetes, CVD, eGFR >30 ml/min/1.73m2
• New micro/macroalbuminuria, 2 X Scr, ESRD, death from renal disease
eGFR according to MDRD formula. Pre‐specified mixed model repeated measures analysis in patients treated with ≥1 dose of study drug who had a baseline and post‐baseline measurement.MDRD, Modification of Diet in Renal Disease.
2323 2267 2205 2121 2064 1927 1981 1763 1479 1262 1123 977 731 448
12Baseline
4
EmpagliflozinPlacebo
28 52 94 10880 12266 136 150 164 178 192
Patients analyzed
4644 4533 4451 4318 4225 4018 4131 3710 3103 2654 2387 2087 1623 1037
24
eGFR Over 192 Weeks
FDA Safety Communication (Dec. 4, 2015): SGLT2 inhibitors to include warnings about DKA and serious UTIs
• FDA Adverse Event Reporting System database identified 20 cases of acidosis reported as diabetic ketoacidosis (DKA), from SGLT2 inhibitors from 3/2013 to 6/2014.
• Not typical for DKA, most had type 2 DM and blood sugar levels, , were only slightly increased compared to typical cases of DKA
• 19 cases of urosepsis and pyelonephritis that started as urinary tract infections with the SGLT2 inhibitors.
Full analysis set. EAC‐confirmed microvascular events including events with onset between date of randomization and date of follow‐up. Cox proportional‐hazard model adjusted for treatment. Development of diabetes‐related blindness was not analysed as an individual component as only one event was observed. *New onset of persistent macroalbuminuria: urine albumin ≥300 mg/g creatinine. †Persistent doubling of serum creatinine level and eGFR ≤45 mL/min/1.73m2 per MDRD. CI: confidence interval; EAC: event adjudication committee; eGFR: estimated glomerular filtration rate; MDRD: modification of diet in renal disease. Presented at 52nd EASD Annual Meeting, 14 September 2016, Munich, Germany.
Hazard ratio(95% CI)
Liraglutide Placebo
N % N %
Number of subjects 4668 100 4672 100
Microvascular endpoint 0.84 (0.73 ; 0.97) 355 7.6 416 8.9
Nephropathy 0.78 (0.67 ; 0.92) 268 5.7 337 7.2
New onset of persistent macroalbuminuria*
0.74 (0.60 ; 0.91) 161 3.4 215 4.6
Persistent doubling of serum creatinine† 0.89 (0.67 ; 1.19) 87 1.9 97 2.1
Need for continuous renal replacement therapy 0.87 (0.61 ; 1.24) 56 1.2 64 1.4
Death due to renal disease 1.59 (0.52 ; 4.87) 8 0.2 5 0.1Hazard ratio (95% CI)
Favors placeboFavors liraglutide
1.0 10.00.1
Microvascular End Points
60 yo diabetic man comes as a new patient. He has HTN.On exam, BP 156/88 mmHg, P 78. He is obese.
Urine ACR: 1800mg/g, eGFR 31 ml/min/1.73m2
Which of the following is the most accurate statement?1. Dietary changes will not alter acidosis.2. Bicarbonate therapy may slow CKD progression.3. Goal CO2 is 28 mEq/L to improve cardiovascular status.
Na K Cl tCO2 BUN SCr GLU139 5.2 112 17 54 2.2 234
GFR and Acid Excretion
+ + = Normal GFR and acid excretion
SNGFR SNGFR SNGFR
+ +CKD ‐↓GFR and acid excretion=
Acid Excretion
Metabolic AcidosisRemaining nephrons need to increase acid excretion
Endothelin NH4+ Aldosterone
Kidney Fibrosis
Acidosis and CKD Progression
Alkali
134
67 62
No Bicarbonate Bicarbonate(1 –3 gm/d)
Study Population:Aged 18‐75 yrsCrCl 15‐29 ml/min/1.73m2 (Stage 4)HCO3 16‐20 mmol/l (nl 22‐26)
Exclusion Criteria:Uncontrolled HTN, fluid overload/CHF
Metabolic Acidosis‐ Open Label Prospective RCT (2 yr f/u)
de Brito‐Ashurst et al. JASN 2009;20:2075‐2084
12.00
14.00
16.00
18.00
20.00
22.00
24.00
0 6 12 18 24
Average CrCl – During the Study
Months
mls/m
in P<0.05 P<0.05 P<0.0001
Bicarbonate
Control
de Brito‐Ashurst et al. JASN 2009;20:2075‐2084
0
5
10
15
20
25
Control Study
33%
6%
p< 0.001
Prop
ortio
n of patients o
n dialysis
Number of Patients with ESRD During Study
Control Bicarbonate
de Brito‐Ashurst et al. JASN 2009;20:2075‐2084
Is more always better? Unadjusted Event Rates by Quartile of Serum Bicarbonate (mEq/L)
Dobre M, et al. AM J Kidney Dis.62:670‐8, 2013.
Metabolic Acidosis
• Apparent at GFR < 25‐30 ml/min, but can occur earlier– Higher animal protein diet →more acid load
• Treatment slows CKD progression• As far as BP, sodium bicarbonate = sodium chloride • Goal serum bicarbonate > 22 mEq/L, Start 0.5‐1 mEq/kg/d
– Sodium bicarbonate tablets • 325 mg (3.9 mEq) or 650 mg (7.8 mEq) tablets
– Sodium citrate solution • 1 mEq/ml
– Baking soda• 54 mEq/level teaspoon
Blood Pressure and CKD Progression
• BP Control more important than which agents are used–Avoid side‐effects
• With proteinuria: ACEi or ARB + diuretic• No proteinuria: no clear drug preference
– ACEi or ARB ok to use
Fujisaki K, et al. Hypertens Res. 2014;37:993‐998.
My friend from school asked me to see her mother, a 72 year old woman with an eGFR of 49 ml/min/1.73m2 and urine ACR of 80 mg/g. Her BP is 130/72 mmHg with longstanding HTN. She feels great. Exam is otherwise unremarkable. Would you advise me to add another anti‐hypertensive medication?
1. Yes2. No
36
9361 participants
StandardSBP <140 mm Hg
IntensiveSBP <120 mm Hg
SPRINT – Major Inclusion Criteria
• > 50 years of age• SBP: 130 – 180 mm Hg (treated or untreated)• >1 other cardiovascular disease (CVD) risk factor
– Clinical or subclinical CVD (excluding stroke)– Chronic kidney disease (CKD),
eGFR between 20‐59 ml/min/1.73m2
– Framingham Risk Score for 10‐year CVD risk ≥ 15%– Age ≥ 75 years
SPRINT – Major Exclusion Criteria
• Stroke
• Diabetes
• Proteinuria >1 gram/day
• eGFR < 20 ml/min/1.73m2 (MDRD)
• Congestive heart failure (symptoms or EF < 35%)
• Adherence concerns
• Polycystic kidney disease
CKDCV Events in SPRINT
40
MI, ACS, stroke, CHF, CV death
Entire Cohort
Hazard
Follow‐up Years
CKD Subgroup
Std
Int
Cheung AK et al. J Am Soc Nephrol 2017;28:2812‐23
Event number ‐ 15 (0.57%) in the intensive treatment group 16 (0.60%) in the standard treatment group
HR 0.90 [0.44‐1.83]; p=0.77
Primary Renal Outcome in the CKD CohortESRD or 50% decline in GFR
Cheung AK et al. J Am Soc Nephrol 2017;28:2812‐23
Agarwal R. J Am Heart Assoc 2017;6:e004536
Bland–Altman plot showing the mean differences between various blood pressure (BP) recordings and their limits of agreement.
SPRINT Trial
‐12.7 mmHg in research vs. clinic
‐12.0 mmHg in research vs. clinic
Systolic
Diastolic
N= 275
‐46 to +20.7 mmHg
‐33.2 to +17.4 mmHg
AHA/ACC HTN Guidelines
<130/80 mmHg
UACR>300 mg/gACEi, ARB
Lipid Disorders in CKD• Use statin (or statin + ezetimibe) if > 50 yo with CKD 3‐5(ND)• If < 50 yo use statin if history of known CAD, MI, DM, stroke
Kidney Disease: Improving Global Outcomes (KDIGO) Lipid Work Group. Kidney Int Suppl. 2013;3:259‐305.http://kdigo.org/home/2013/11/04/kdigo‐announces‐publication‐of‐guideline‐on‐lipid‐management/
Survival Curves of CKD Patients with f/u SBP < 120 vs. 120‐139 mmHg with ↑BP meds
Covesdy CP et al. JAMA Int Med 2014;174:1442‐1449
N=5760
N=5760
Slowing CKD Progression: ACEi/ARB• Check labs after initiation
–< 25% SCr increase, continue and monitor–> 25% SCr increase, stop ACEi and evaluate for RAS
• Continue until contraindication arises (hyperkalemia), no absolute eGFR cutoff
• Better proteinuria suppression with low Na diet and diuretics• Avoid volume depletion
Lipid Disorders in CKD
17% reduction in primary outcome (nonfatal MI, coronary death, nonhemorrhagic stroke, arterial revascularization)
No reduction in CKD progressionBaigent C, et al. Study of Heart and Renal Protection (SHARP). Lancet. 2011;11:60739‐60743.
Why do we care about phosphate? Arterial Medial Calcification in CKD
Adapted from London et al, NDT 2002
↑FGF23 for Hyperphosphatemia – CV Issues?Chronic Renal Insufficiency Cohort (N = 3,070 w/ ECHO)
49
Pharmacological FGFR4 Blockade Protects 5/6 Nephrectomized Rats from Developing LVH
*P < 0.001; N = 6–14 per group
anti‐FGFR4, i.p. inj, after surgery every 3 days for 14 days
Grabner A et al. Cell Metab. 2015
How often do we do CKD‐MBD testing?
CKD Stage Calcium, Phosphorus
PTH25(OH)D
Stage 3 Every 6‐12 months
Once then based on CKD
progressionOnce, then based on level and treatments
Stage 4 Every 3‐6 months Every 6‐12 months
Stage 5 Every 1‐3 months Every 3‐6 months
Use CKD progression, presence or absence of abnormalities, treatment response and side effects to guide testing frequency.
KDIGO Guideline. Kidney Int. 2009;76 (113):S1‐S130.
The Renal Diet
52
CKD‐Mineral and Bone Disorders (CKD‐MBD) – A lot of opinions
• Keep serum phosphorous in normal range– Limit phosphorus in diet, decrease packaged products ‐ Refer to dietitian– May need phosphate binders with meals
• Vitamin D2 if serum 25(OH) vit D level <30 ng/mL– Cholecalciferol 800‐2000 IU daily to achieve normal serum levels
• Treat with active oral vitamin D if serum 25(OH) vit D >30 ng/mL and iPTH is above target range (normal up to stage 4, 2‐9 x no for stage 5) – Calcitriol: 0.25 mcg 3x/wk‐daily– Doxercalciferol: 2 mcg 3x/wk‐daily– Paricalcitol: 2 mcg 3x/ wk‐daily
• DEXA doesn’t predict fracture risk well in CKD 4‐5
Phosphate BindersBinder Advantages Disadvantages Cost
Aluminumhydroxide
Very effective • Aluminum toxicity (adynamic bone disease & dementia)
$
Calciumcarbonate
Effective, comes in liquid or chewable
• Calcium load• GI side effects
$
CalciumAcetate
As effective as CaCO3 • Potentially less calcium load• GI side effects• Potential ↓ tetracycline &
fluoroquinolone
$$
SevelamerCarbonate
Effective, no calcium load, potentially better acid‐base balance, comes in powder
• GI side effects, bowel obstruction• ↓absorption of fat‐soluble vitamins?• ↓ fluoroquinolone?
$$
LanthanumCarbonate
Effective, no calcium load, comes in chewable form
• Potential for systemic accumulation • GI side effects
$$$
KDIGO Guideline. Kidney Int. 2009;76 (113):S1‐S130.
HYPERKALEMIA
Who gets Hyperkalemia? Characteristics Odds Ratio 95% CIEither ACEi/ARB 1.41 1.37, 1.44Diabetes 1.51 1.47, 1.55CKD Stage
3 2.24 2.17, 2.304 5.91 5.63, 6.205 11.00 10.34, 11.69
Einhorn LM, et al. Arch Intern Med 169:1156‐62, 2009.
Drug‐Induced Hyperkalemia in CKDMechanisms DrugsImpairs Renin –Angiotensin ‐Aldosterone function
ACEi/ ARBs, β‐blockersHeparin (SQ, LMW) NSAIDs, COX‐2 inhibitors
Altered K+ distribution β‐blockers
Increased K+ load Salt substitutes, K+ or herbal supplementsPRBC infusions
Reduced K+ excretion K+ sparing diureticsCalcineurin inhibitorsTMP‐SMX, pentamidine
Chronic Management of Hyperkalemia• Low K+ diet 2000 mg/d (~50 mEq/d) vs. normal 4500 mg/d
Diet sheets from National Kidney Foundation kidney.org
Chronic Management of Hyperkalemia• Thiazide or loop diuretics
– Select loop diuretics if eGFR <30 ml/min
• If acidotic, correct acidosis with oral bicarbonate
• If starting ACE‐inhibitor or ARB
– Start low dose
– Check serum K+ within 1 week of initiation or dose escalation
• Exchange resins: Sodium polystyrene sulfonate– Theoretical: Bound Na+ exchanged for K+ in colon/rectum
– Likely: Accompanying sorbitol induces diarrhea
– Usually requires multiple doses
Colonic Necrosis from Sodium Polystyrene Sulfonate in 70% Sorbitol
By 2005 the FDA had received 35 reports of serious bowel injuries associated with both oral and rectal administration of the mixture, many were fatal.
Chou, Y.H. Kaohsiung J Med Sci. 2011
Serum K+(mEq/L) 5.1 to 5.4 5.5 to 6.4
Starting Dose(Gms) 4.2 bid8.4 bid
Concerns about Patiromer• Hypomagnesemia
– 8.6% Mg < 1.4 mg/dl– 4.3% Mg < 1.2 mg/dl
• 9/13 had Mg <1.8 mg/dl on entry• 8/13 on diuretics or PPI’s
• Calcium load – No difference in serum calcium– Is there positive calcium balance?– Long term risk of ectopic calcifications?
• Cost $595 per month, not for acute treatment• Black box warning issued about drug‐drug interactions
– 3 hours between Patiromer & other drugs
CKD Progression: Biology versus “Iatrogenesis”?
time
NSAID for Gout
Gentamicin forUTI
Contrast forcoronary cath
CHF with diuresisleading to AKIand low BP
GFR
Baseline rate of decline in GFR
ESRD
time
NSAID for Gout
Gentamicin forUTI
Contrast forcoronary cath
CHF with diuresisleading to AKIand low BP
GFR
Baseline rate of decline in GFR
ESRD
Fink, et al, AJKD, 2009
CKD Progression: Biology versus “Iatrogenesis”?
time
NSAID for Gout
Gentamicin forUTI
Contrast forcoronary cath
CHF with diuresisleading to AKIand low BP
GFR
Baseline rate of decline in GFR
ESRD
time
NSAID for Gout
Gentamicin forUTI
Contrast forcoronary cath
CHF with diuresisleading to AKIand low BP
GFR
Baseline rate of decline in GFR
ESRD
Fink, et al, AJKD, 2009
DRUG‐RELATED ADVERSE SAFETY EVENTS IN CKD
Rate of adverse drug events in ambulatory patients with CKDN=267 Rate (per 100 patients)*
PATIENT REPORTEDHypoglycemia 57.6
Falling/ severe dizziness 23.1
Nausea, vomiting ± diarrhea 21.1
Hyperkalemia 18.1
Confusion 16.9
DETECTED AT STUDY VISITHypoglycemia 8.3
Hyperkalemia 8.3
Bradycardia 6.4*Adjusted for sociodemographics, comorbid conditions, GFR, and number of medications
Adapted from Ginsberg JS, et al. J Am Soc Nephrol 2014.
Case Presentation
74 yo woman with right hip pain. Two wks earlier Scr 1.3 mg/dl. Fell and was admitted. Scr 1.9 mg/dl. Given IVF and discontinued HCTZ, ibuprofen and irbesartan. Urinalysis‐ ATN. More hip pain. Tramadol 50 mg qd. ↑Gapabentin 300 tid. 5 days after admission: Na 132 mEq/l, BUN 50 mg/dl, Scr 2.8 mg/dl. She has ↑drowsiness + asterixis. What is contributing most to her sxs and signs and what should we do?1. Dialysis for uremia2. D/c tramadol, give naloxone3. D/c gabapentin4. Treat hyponatremia
• Mayo clinic – 33/594 with GFR < 90 ml/min developed side effects• 7/9 ESRD patients had side effects
Gabapentin
CrCl (mL/min)Total daily dose
(mg) Dosage regimen> 60 1,200 400 mg TID31 – 60 600 300 mg BID15 – 30 300 300 mg QD
< 15 150 300 mg QOD
Hemodialysis — 200 – 300 mg post‐HD
70
Loading dose: 300 – 400 mgMaintenance dose: 200 – 300 mg after each 4‐h HD session
Common Medications Requiring DoseReduction in CKD
• Allopurinol• Gabapentin, pregabalin• Metoclopramide
o Reduce 50% for eGFR< 40o Can cause irreversible EPS
• Narcoticso Methadone and fentanyl best for ESRD ‐
Lowest risk of toxic metabolites
• Renally cleared beta blockerso Atenolol, bisoprolol, nadolol
• Digoxin
• Some Statinso Lovastatin, pravastatin, simvastatin. Fluvastatin, rosuvastatin
• Antimicrobialso Antifungals, aminoglycosides, Sulfamethoxazole/Trimetroprim, Nitrofurantoin
• Enoxaparin
• Methotrexate
• Colchicine
KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral • GFR <30 ml/min/1.73m2
• Proteinuria > 0.5‐1.0 g/d despite ACEi or ARB therapy
• Atypical/rapid progression of CKD o > 5 ml/min/1.73m2/yearo > 25% fall in baseline eGFR
• Red cell casts, RBC > 20/HPF sustained and not readily explained
• Hypertension refractory to > 4 antihypertensive agents
• Persistent abnormalities of serum potassium
• Recurrent or extensive nephrolithiasis
KDIGO controversies conference report. Kidney Int 2011; 80: 17‐28;
When to Refer
When to Refer• Early vs. Late Referral
– Renal replacement therapy < 3 mo after referral to Nephrology
• Chan et al. – Meta‐analysis of 22 studies evaluating early vs. late referral
75
Early Referral Avoids “Access of Evil”
Infection
Late Referral 80% of hemodialysis patients start with a dialysis catheter
Primary/Subspecialty Care TEAM
Partner with Primary Care Colleagues
Conclusions
• Use GFR estimating equations• Stage CKD with eGFR and albuminuria and consider cause• Control BP…but goal is not clear• Not everyone with CKD needs RAAS blockade• Manage DM, HTN, acidosis to decrease progression• Avoid nephrotoxins• CKD means CV risk factor.
