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Chronic Kidney Disease (CKD): An Update for the Primary Physician

Chronic Kidney Disease (CKD): An Update for the Primary Physician. Joshua Augustine, M.D. Wade Park Veterans Administration Hospital 1/28/14. Quiz Questions. 1.Name the two formulas that are best at estimating glomerular filtration rate (GFR) in patients with CKD.

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Chronic Kidney Disease (CKD): An Update for the Primary Physician

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  1. Chronic Kidney Disease (CKD):An Update for the Primary Physician Joshua Augustine, M.D. Wade Park Veterans Administration Hospital 1/28/14

  2. Quiz Questions 1.Name the two formulas that are best at estimating glomerular filtration rate (GFR) in patients with CKD. 2.At what stage of CKD should all patients be referred to a nephrologist? 3.Name three situations that may warrant a nephrology referral at lower stages of CKD

  3. Chronic Kidney Disease: Definition • Kidney damage for ≥ 3 months, as defined by structural or functional abnormalities • Pathological abnormalities • Markers of kidney damage by blood, urine, or imaging tests • GFR < 60 ml/min/1.73 m2 for > 3 months, with or without kidney damage

  4. Risk Factors for CKD • Diabetes • Hypertension • Autoimmune diseases • Systemic infections • Exposure to drugs associated with acute decline in kidney function • NSAIDs • Contrast agents • Recovery from acute kidney failure • Age > 60 years • Family history of kidney disease • Reduced kidney mass • Smoking National Kidney Foundation. Am J Kidney Dis. 2002;39(suppl 1):S17-S31. Pinto-Sietsma SJ, et al. Ann Intern Med. 2000;133:585-591.

  5. Etiology of Chronic Kidney Disease • Diabetic glomerulosclerosis • Type I or II 33% • Glomerular disease (primary or secondary) 19% • Vascular disease and hypertension • Including sickle cell and HUS 21% • Tubulointersitial disease • Pyelonephritis, analgesic, allergic 4% • Cystic disease • Polycystic, medullary cystic 6%

  6. Stage 1: Normal GFR; GFR >90 mL/min/1.73 m2 with other evidence of chronic kidney damage* Stage 2: Mild impairment; GFR 60-89 mL/min/1.73 m2 with other evidence of chronic kidney damage* Stage 3: Moderate impairment; GFR 30-59 mL/min/1.73 m2 Stage 4: Severe impairment: GFR 15-29 mL/min/1.73 m2 Stage 5: Established renal failure: GFR < 15 mL/min/1.73 m2 or on dialysis * “Other evidence” may be one of the following: • Persistent microalbuminuria/proteinuria • Persistent hematuria from a renal origin • Structural abnormalities of the kidneys demonstrated on ultrasound or other radiological tests • Biopsy-proven inflammation or fibrosis Chronic Kidney Disease Stages

  7. Prevalence of CKD in NHANES* 1999-2004 participants *National Health and Nutrition Examination Survey, n=12,785 age ≥ 20 y/o By MDRD formula, USRDS 2010

  8. Kidney Disease in African Americans • African Americans make up about 12% of the population but account for 32% of people with kidney failure • Among new patients whose kidney failure was caused by high blood pressure, more than half (51%) are African American • Among new patients whose kidney failure was caused by diabetes, almost 1/3 (31%) are African American • African-American men ages 20-29 and 30-39 are 10 x and 14 x more likely to develop kidney failure due to high blood pressure than Caucasian men in the same age group

  9. Progressive CKD is Associated with Cardiovascular Risk

  10. Death ESRD Current CKD Outcomes: Death vs. ESRD n = 40,250 D = diabetes ND = no diabetes Adaptedfrom US Renal Data System. USRDS 2002 Annual Data Report: Atlas of End-Stage Renal Disease in the United States. National Institutes of Health. 2002. Available at: www.usrds.org/atlas.htm.

  11. But ESRD is More Common than Death in Blacks with Hypertensive Kidney Disease AASK Trial, 1/3 of patients were < 50 y/o at enrollment J Am Soc Nephrol 21: 1361-9, 2010

  12. Kidney Disease Improving Global Outcomes (KDIGO) (Kidney Int 2013) • New CKD guidelines from 2013 • New staging concept: GFR and albuminuria categories • GFR categories add “G3a” for GFR 45-59, “G3b” for GFR 30-44 • Albuminuria categories:

  13. Estimating renal function • Abbreviated MDRD equation = • CKD-EPI equation = 186 x (SCr)-1.154 x (Age)-0.203 x (0.742 if female) x (1.210 if Black)

  14. Estimated GFR • Google: “MDRD Calculator” • http://www.nephron.com/MDRD_GFR.cgi • Save to your favorites! • More recent CKD EPI equation is less likely to underestimate GFR in patients with higher GFR

  15. MDRD vs. CKD-EPI EquationNHANES data 2003-2006 USRDS 2010

  16. Cystatin C • A low molecular weight cysteine protease inhibitor- produced by all nucleated cells • Filtered at the glomerulus and not reabsorbed • However, metabolized in the tubules • Inflammation, thyroid disease, and steroids may affect levels • Less dependent on race and body mass • Potetential uses: • Confirming stage 3a CKD (eGFR 45-59 ml/min) • KDIGO: if cystatin C formula > 60, patient should not be labeled as having CKD • Assessing for CKD in malnourished patients

  17. Testing for CKD and Monitoring Progression • Regular testing of patients at risk with: • Diabetes • Hypertension • Family history of kidney failure • Cardiovascular disease • Rapid progression is considered a decline of more than 5 ml/min/1.73m2/yr

  18. Graphing glomerular filtration rate 59 y/o with autosomal dominant polycystic kidney disease 51 y/o with severe acute and chronic interstitial nephritis

  19. Screen for Proteinuria • As part of the initial assessment of patients with: • Diabetes mellitus • Newly discovered GFR < 60 ml/min/1.73 m2 • Newly discovered hematuria • Newly diagnosed hypertension • Unexplained edema • Suspected heart failure • Suspected multisystem disease, e.g. lupus

  20. Screening for Proteinuria: Spot Sample is Recommended • KDIGO recommends albumin:creatinine ratio • Better laboratory precision than protein:creatinine • May also check spot total urine protein to creatinine ratio or 24 hr urine • Test a.m. samples • Avoid testing in febrile patient or after vigorous exercise • Confirm with repeat testing

  21. Treatment of Hypertension: KDIGO • Recommended that all CKD patients with no proteinuria have a target BP ≤ 140/90 • Goal blood pressure for all CKD patients with any degree of proteinuria: ≤ 130/80 (JNC8-140/90) • ARB or ACEI first line for any diabetic with abnormal proteinuria, and for any CKD patient with albumin excretion • ACEI/ARB combination not recommended

  22. Intensive blood pressure control in non-diabetic blacks with CKD: benefit in subgroup with proteinuria N Engl J Med 363: 918-29, 2010

  23. Referral to Nephrology • All patients with GFR <30 mL/min/1.73m2 (Stage 4) should be referred to a nephrologist • Additionally refer stage 3 CKD with: • Younger Age • Poorly controlled blood pressure • Declining kidney function • Hyperkalemia on acei/arb therapy • Proteinuria DeCoster C et al. J Nephrol 23: 399-407, 2010

  24. Late Referral to Nephrology • Often defined as referral at < six months prior to initiation of dialysis therapy • Historically the case for 30-50% of patients • Typically leads to inpatient dialysis (often urgently) with a vascular catheter • Associated with increased one year morbidity and mortality • High rate of infection, line sepsis Nephrol Dial Transplant 20: 490-6, 2006

  25. Late Referral to Nephrology • Causes: • Fulminant renal failure • Lack of access to any medical care • Emergency room presentation • Patient failure to follow through with referral • Older patient with plans for conservative management of uremia • However, most older patients choose dialysis Nephrol Dial Transplant 20: 490-6, 2006

  26. Case #1 • 77 y/o white female with longstanding diabetes and 2+ proteinuria, Cr 2.4 • eGFR = 20 ml/min/1.73m2 • Patient states she is “not interested” in dialysis • Who is? • Cr appears stable, so decision made not to refer • Three months later, patient hospitalized with CHFrequiring diuresis • Cr on f/u testing is 3.3 • eGFR=14 ml/min/1.73m2 • Patient agrees to dialysis if necessary

  27. Survival in the Elderly: Dialysis vs. Conservative Management • UK study of 202 patients > 70 y/o with stage 5 CKD • 173 chose dialysis, 29 chose conservative management • Median survival 37.8 mos (range 0 to 106) for dialysis vs. 13.9 mos (range 2 to 44) for conservative management • But dialysis patients spent more time in the hospital relative to days of survival and were more likely to die in the hospital Clin J Am Soc Nephrol 4:1611-9, 2009

  28. Survival in the Elderly: Dialysis vs. Conservative Management Clin J Am Soc Nephrol 4:1611-9, 2009

  29. Hypertension • Can consider nephrology referral if blood pressure > 150/90 despite usage of three antihypertensive drugs from different classes • ACE inhibitors or ARBs are first line in any patient with proteinuria/albuminuria • Diuretics key to blood pressure control • Thiazide if eGFR >30 • Loop diuretics for lower GFR • May need 4-5 agents, varied timing, bedtime dosing

  30. Ambulatory Blood Pressure Monitoring in CKD • VA study of 217 CKD patients stage III to V (pre-ESRD) with abnormal urinary protein • Clinic BP vs. 24 hr. ambulatory monitoring • Correlated measurements with ESRD and death • Occurred in 34.5% over a median of 3.5 yrs • Systolic blood pressure correlated with primary outcome • But normal home BP more predictive of renal outcomes in patients with high clinic BP Kidney Int. 69: 1175-80, 2006

  31. Predictive value of ambulatory BP in patients with high clinic BP n=95 n=51 Kidney Int. 69: 1175-80, 2006

  32. Correlation of non-dipping with ESRD Kidney Int. 69: 1175-80, 2006

  33. Diabetic Nephropathy • “Microalbuminuria” defines the onset • Urinary albumin excretion of 30-300 mg/day • Spot urinary albumin:creatinine ratio > 30 mg/g Cr • Persistent elevation of urinary protein in the absence of other kidney disease • Consider referral when proteinuria is increasing, even with normal creatinine

  34. Natural history of diabetic nephropathy d Hyperfiltration Microalbuminuria

  35. Type II DM: IDNT (Irbesartan in Diabetic Nephropathy) Trial(NEJM 2001; 345:851-60)

  36. Addition of the Aldosterone Inhibitor Spironolactone to ACE Inhibitor in Diabetic Nephropathy *Potassium level ≥ 6 meq/L occurred in 14/27 (52%) on spironolactone J Am Soc Nephrol 20: 2641-50, 2009

  37. Preventing hyperkalemia with angiotensin blockade • Introduce agents at low dose • Check labs 1 week after initiation/dose change • If adding spironolactone or eplerenone, do not exceed 25 mg/day • Avoid if GFR is < 30 ml/min or potassium >5.0 mmol/L • Diuretics can increase distal sodium delivery and potassium excretion • Loop diuretics if GFR < 30 ml/min • Avoid volume depletion with diuretics, which may worsen hyperkalemia NEJM 2004; 351:585-592

  38. Possible scenarios of change in creatinine after angiotensin blockade Volume depletion, CHF, NSAIDs or RAS Stable CKD Normal kidney function Arch Intern Med 2000 160:685-693

  39. Anemia Treatment in CKD-KDIGO • Intravenous iron usage is encouraged • With TSAT up to 30% and ferritin up to 500 ng/ml • Avoid with acute infection • Based on animal data demonstrating impaired response to infection • Do not initiate ESA therapy unless Hb < 10 g/dl • Goal: to avoid Hb < 9 g/dl and Hb > 11.5 g/dl • Avoid escalation in resistant patients to greater than double the weight-based recommended dosage • Use with great caution in patients with active malignancy or history of CVA

  40. Caveats on Treating Anemia in CKD • TREAT trial • Randomized 4038 patients with DM and CKD • Mean age 68 yrs, median eGFR 33 ml/min/1.72m2 • Median follow-up 29 months • Darbepoetin treatment: • Target Hb of 13 g/dL vs. watchful waiting and rescue Tx for Hb < 9 g/dL • Achieved Hb level: 12.5 vs. 10.6 g/dL • No difference in death, CHF, or time to ESRD New Engl J Med 361: 2019-32, 2009

  41. Caveats on Treating Anemia in CKD • TREAT trial • Slight improvement in fatigue score in treated group • More transfusions in untreated group • 24.5% vs. 14.8% (p<0.001) • Greater stroke risk in treated group • 5% vs. 2.6%, hazards ratio 1.92 (1.38 to 2.68, p<0.001) • Also greater risk of venous and arterial thrombosis New Engl J Med 361: 2019-32, 2009

  42. Lipid Lowering: SHARP trial • Study of Heart and Renal Protection • 9270 patients ≥ 40 y/o with CKD • SCr ≥ 1.7 mg/dl in men, ≥ 1.5 mg/dl in women • 1/3 of patients had ESRD • Randomized to simvastatin 20 mg/d + ezetimibe 10 mg/d vs. placebo • F/U average 4.9 yrs • Analyzed rate to first major atherosclerotic event (MI, coronary death, CVA or arterial revascularization) • 11.3% vs. 13.4% (rr=0.83, 95% CI: 0.74 to 0.94, p=0.002) Lancet 377: 2181-92, 2011

  43. SHARP Trial Lancet 377: 2181-92, 2011

  44. SHARP Trial Lancet 377: 2181-92, 2011

  45. Lipid Lowering: SHARP trial • Subgroup analysis showed statistical difference only in non-dialysis cohort • No affect on mortality • No affect of progression of CKD • Well tolerated, no increase in myopathy or other s.e.’s

  46. Monitoring Markers of Bone Mineralization: When to Refer? • CKD stage III: • Check Serum Ca, Phos, PTH annually • Phos goal: 2.7 to 4.6 mg/dL • PTH goal 35 to 70 pg/mL • If high: check 25 vitamin D • Treat low 25 vitamin D with ergocalciferol • Monitor Ca and Phos on vitamin D therapy • Repeat PTH and 25 vitamin D in six months • If persistent elevation in phos or PTH: • Refer to nephrology for dietician, binders or calcimimetic therapy

  47. Lifestyle and Dietary Goals • BMI 20-25 kg/m2 • < 2 g Sodium/day (<5 g NaCl) • Protein 0.8 gm/kg/day • Exercise: goal 30 minutes 5x/week • EtOH no more than 2/d men, 1/d women

  48. Preparing for Hemodialysis Access • When GFR <45 (CKD stage 3b) the patient should be educated about saving veins in non-dominant arm (avoid needle sticks and BP checks) • When GFR <30 (CKD Stage 4) and patient chooses hemodialysis, nephrologist should refer to surgeon for AV fistula consultation. • Best for AV fistula to be created 6 months to 1 year prior to dialysis start to allow for maturation time • Goal should be to avoid hemodialysis catheter whenever possible.

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