8/9/2019 Disclosures CHRONIC KIDNEY DISEASE UPDATE: WHAT THE GENERALIST NEEDS TO KNOW I am on the Scientific Advisory Boards with stock option compensation for the following companies: MICHAEL G. SHLIPAK, MD, MPH TAI Diagnostics SCIENTIFIC DIRECTOR , KIDNEY HEALTH RESEARCH COLLABORATIVE Cricket Health, Inc. PROFESSOR OF MEDICINE, EPIDEMIOLOGY & BIOSTATISTICS UNIVERSITY OF CALIFORNIA, SAN FRANCISCO ASSOCIATE CHIEF OF MEDICINE FOR RESEARCH DEVELOPMENT SAN FRANCISCO VA MEDICAL CENTER August 8, 2019 Outline Outline Definition and Complications Definition and Complications New CKD Staging 2013 New CKD Staging 2013 Screening for CKD Screening for CKD Introduction to Cystatin C Introduction to Cystatin C Treatment of CKD Treatment of CKD Hyperkalemia Hyperkalemia 1
8/9/2019 Question 1: Which of these patients has CKD? Heart failure patient in ED with creatinine A. DEFINITION & CLASSIFICATION of 2.0 OF CHRONIC KIDNEY DISEASE 44% Diabetes patient with albumin/creatinine B. 35% of 100 mg/g, creatinine= 1.0 mg/dL KDIGO 2012 Clinical Practice Guideline (CPG) for the Evaluation and Management of Chronic Kidney Disease 35 year old African American man with 15% C. Kidney inter., Suppl. 2013; 3: 1–150 creatinine of 1.5 6% All of the above D. e . v . . . . . . . o n r b h e i t m a t i n w A e e h i t n t t n a a f p e c o i i e t r l a f A l r A u p d i l s a e o l f t t e r r b a a e a e i y H D 5 3 Introduction Definition and Complications Overall CKD definition unchanged Chronic Kidney Disease (CKD): Defined in 2002 with original CKD staging Chronic kidney disease: >3 month duration of either: Decreased kidney function (GFR<60) Replaced earlier terms “chronic renal insufficiency”, Injury/damage to the kidney (e.g. albuminuria, cysts, stones) “chronic renal failure”, or “high creatinine” Etiology of CKD: Previous 5 CKD stages were developed by an expert Common diseases treated by generalists: diabetes, hypertension, a) panel cardiovascular disease, heart failure Other systemic diseases typically treated by specialists : systemic Most CKD epidemiology research has been conducted b) lupus erythematosus, HIV, urological diseases since the 5 stages were defined Primary kidney disease: polycystic kidney disease, glomerular c) disease 2
8/9/2019 Prognosis by eGFR and Albuminuria Complications of CKD Kidney failure (end-stage renal disease) Key meta-analysis published in 2010 in Lancet Death Evaluated prognosis by eGFR and albuminuria Other chronic disease: 21 studies, 1.2 million patients Atherosclerotic Cardiovascular Disease Heart failure Predictor: Osteoporosis/fracture eGFR categories Cognitive impairment/dementia Albuminuria (ACR categories) Frailty Outcome: mortality risk Treatment Complications: Medications Procedures Albuminuria and eGFR grid ESRD Risk Chronic Kidney Disease Prognosis Consortium . Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality : a collaborative meta-analysis. Lancet 2010 Kidney Failure Equation: kidneyfailurerisk.com AGE, SEX, RACE and CARDIOVASCULAR RISK FACTOR ADJUSTED HAZARD RATIO for All-cause Mortality Albuminuria Classes (mg/g) <10 10-29 30-300 >300 All Albuminuria Classes (mg/g) <10 10-29 30-300 >300 All >105 1.0 1.4 0.1 4.4 1.2 >105 1.0 1.4 2.0 4.4 1.2 90-104 1.0 1.3 0.1 3.1 1.0 eGFR 75-89 0.9 1.2 0.1 2.5 1.0 90-104 1.0 1.3 1.5 3.1 1.0 (mL/min/ 60-74 0.9 1.2 0.3 3.0 1.3 eGFR 75-89 0.9 1.2 1.7 2.5 1.0 1.73m 2 ) 45-59 0.1 0.8 1.4 5.3 0.3 (mL/min/ 60-74 0.9 1.2 1.8 3.0 1.3 30-44 1.7 2.1 9.2 4.4 4.0 1.73m 2 ) 45-59 1.2 1.5 1.9 3.4 2.0 15-29 4.0 3.0 37.7 6.0 3.6 30-44 1.7 2.1 3.0 4.4 4.0 All 1.0 1.3 1.6 3.6 15-29 4.0 3.0 4.2 6.0 3.6 *P<0.05 All 1.0 1.3 2.0 3.6 *P<0.05 CKD Prognosis Consortium. Lancet: 2073-81. 2010 CKD Prognosis Consortium. Kidney Int. 2011; 80(1): 93-104 3
8/9/2019 Outline CKD Stages and Prevalence Definition and Complications U.S. Prevalence Estimated GFR CKD Stage N (1000’s) (mL/min per 1.73 m 2 ) New CKD Staging 2013 (%) CKD Stage 1 90+* 3,200 (1.6) Screening for CKD CKD Stage 2 60-89* 6,500 (3.2) Introduction to Cystatin C CKD Stage 3 30–59 15,500 (7.7) Treatment of CKD CKD Stage 4 15–29 700 (0.4) Hyperkalemia CKD Stage 5 <15 (or dialysis) 400 (0.2) * With evidence of kidney damage, e.g. albuminuria KDOQI Guidelines, AJKD, Feb. 2002 Problems with Old Staging From Old to New Staging Stages 1 and 2 were the same CGA Staging (like TMN) replaces the prior 5 stages of CKD U.S. Prevalence Estimated GFR • “CKD” is an inadequate GFR CKD Stage N (1000’s) Stage 3 (30-60) was too broad; eGFR of 30-45 is Cause Albuminuria (mL/min per 1.73 m 2 ) (mL/min per 1.73 m 2 ) descriptor (like diabetes) (%) very different from 45-60 • Hypertensive with eGFR= 50, CKD Stage 1 90+* 3,200 (1.6) Diabetes G1 (>90) A1 (ACR< 30) ACR= 10 Did not address levels of albuminuria; and only Hypertension G2 (60-89) A2 (ACR 30-300) • Diabetic CKD with eGFR= 75, CKD Stage 2 60-89* 6,500 (3.2) used albuminuria for Stages 1 and 2 ACR= 500 Polycystic Disease G3a (45 -59) A3 (ACR > 300) CKD Stage 3 30–59 15,500 (7.7) GN G3b (30 -44) Unknown CKD Stage 4 G4 (15 15–29 -29) 700 (0.4) G5 (< 15) CKD Stage 5 <15 (or dialysis) 400 (0.2) 4
8/9/2019 CGA Staging for CKD Outline Definition and Complications It is recommended that CKD be classified by: New CKD Staging 2013 Cause Screening for CKD GFR category Introduction to Cystatin C Albuminuria category Treatment of CKD Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Hyperkalemia Kidney Disease. Kidney inter., Suppl. 2013; 3: 1–150. Screening for CKD Who to Screen with Urine Albumin? International CKD guidelines do not address when Primary prevention screens: or how to screen Diabetes- annual No RCT evidence for or against Hypertension Relative costs of screening vary by region Elderly Hypertension, Diabetes, and CVD guidelines all CKD Staging: recommend some form of CKD screening. Urine albumin is now important part of CKD staging The following are my suggestions for primary care: Should be measured and documented in all CKD patients Repeat annually in diabetics every 2-3 years in non-diabetics 5
8/9/2019 How to Measure Urine Albumin Who and When to Check Creatinine? Begin screening: Often listed as “microalbumin panel” Age >40 lower-risk populations Focus on albumin/creatinine ratio (ACR): Age >30 Blacks, Native Americans ACR (mg/g) OLD NEW Diagnosis of hypertension, diabetes, cardiovascular < 30 Normal Normal or mildly disease, heart failure elevated 30-300 Microalbuminuria Moderately elevated Frequency of creatinine monitoring (no evidence) No risk factors: 3-5 years >300 Macroalbuminuria Severely elevated Risk factors: 1-2 years Dipstick: “trace” is abnormal Creatinine cost: $0.20 If dipstick is abnormal, quantify ACR Question 3: Which of the following is GFR Estimation from Creatinine true about creatinine GFR estimates? Estimated GFR: More accurate in older populations than A. middle-aged because prevalence of Automatic reporting by most labs kidney disease is higher Equations are rough 75% <60 concerning for kidney disease, but not specific They have been validated in most ethnic B. >60- so imprecise, its considered just “>60” groups 3 equations in current use: They are more likely to be accurate in C. Cockroft-Gault (Nephron, 1976)- used by FDA and healthy persons than in persons with 17% pharmacies 6% chronic illness 3% MDRD (Annals, 1999)- used for most automated reporting CKD-EPI (Annals, 2009)- favored by researchers All of the above e D. . . . v . . . o . e b . . t b a r o a e d t d e l i y h o l a e l t v n k f n o i e l i e l e e l t r A a b o r u e m v c c a e h a r a e y r e y o h e M T h T 6
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