8/7/2013 Outline CHRONIC KIDNEY DISEASE UPDATE: WHAT THE GENERALIST � Definition and Complications NEEDS TO KNOW � New CKD Staging 2013 � Screening for CKD MICHAEL G. SHLIPAK, MD, MPH CHIEF-GENERAL INTERNAL MEDICINE, � Treatment of CKD SAN FRANCISCO VA MEDICAL CENTER PROFESSOR OF MEDICINE, EPIDEMIOLOGY AND � Introduction to Cystatin C BIOSTATISTICS, UCSF � When to refer to nephrologist August 7, 2013 Question 1: Which of these patients has Outline CKD? � Definition and Complications Heart failure patient in ED with creatinine of 2.0 a) � New CKD Staging 2013 Diabetes patient with albumin/creatinine of 100 b) mg/g, creatinine= 1.0 mg/dL � Screening for CKD 35 year old African American man with c) � Treatment of CKD 52% creatinine of 1.5 � Introduction to Cystatin C 35% All of the above d) � When to refer to nephrologist 13% 0% . . . . . . . . e . . . . e A f o r t i b u a d a l p i o l e a s h f e r t t t a r e e f a b y o e a l H i 5 A l D 3 1
8/7/2013 Introduction � Chronic Kidney Disease (CKD): DEFINITION & CLASSIFICATION � Defined in 2002 with original CKD staging OF CHRONIC KIDNEY DISEASE � Replaced earlier terms “chronic renal insufficiency”, “chronic renal failure”, or “high creatinine” KDIGO 2012 Clinical Practice Guideline (CPG) for the � Previous 5 CKD stages were developed by an expert Evaluation and Management of Chronic Kidney Disease panel Kidney inter., Suppl. 2013; 3: 1–150 � Most CKD epidemiology research has been conducted since the 5 stages were defined Definition and Complications Complications of CKD � Kidney failure (end-stage renal disease) � Overall CKD definition unchanged � Death � Chronic kidney disease: >3 month duration of either: � Decreased kidney function (eGFR<60) � Other chronic disease: � Injury/damage to the kidney (e.g. albuminuria, cysts, stones) � Atherosclerotic Cardiovascular Disease � Etiology of CKD: � Heart failure Common diseases treated by generalists: diabetes, hypertension, a) � Osteoporosis/fracture cardiovascular disease, heart failure � Cognitive impairment/dementia Other systemic diseases typically treated by specialists : systemic b) � Frailty lupus erythematosus, HIV, urological diseases Primary kidney disease: polycystic kidney disease, glomerular c) � Treatment Complications: disease � Medications � Procedures 2
8/7/2013 Question 2: A 75 yr. old White male with CAD and HF CKD Complications has an eGFR= 25. What is he at most risk for? Keith et al., Arch Int Med, 2004 • Design: Northwest Kaiser database Death a) •5 year follow-up Dialysis 78% b) •Death and ESRD outcomes eGFR 30-60 eGFR 15-30 N= 11,278 N= 777 Age 72 74 22% ESRD (%), 5 yrs 1 20 Death (%), 5 yrs 24 45 h s i t s a y e l a D D i Albuminuria and eGFR grid Prognosis by eGFR and Albuminuria 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 AGE, SEX, RACE and CARDIOVASCULAR RISK FACTOR ADJUSTED HAZARD � Key meta-analysis published in 2010 in Lancet RATIO for All -cause Mortality � Evaluated prognosis by eGFR and albuminuria Albuminuria Classes (mg/g) Conclusion: CKD staging must integrate eGFR and albuminuria together <10 10-29 30-300 >300 All � 21 studies, 1.2 million patients >105 1.0 1.4 2.0 4.4 1.2 90-104 1.0 1.3 1.5 3.1 1.0 CKD by � Predictor: eGFR 75-89 0.9 1.2 1.7 2.5 1.0 albuminuria (mL/min/ 60-74 0.9 1.2 1.8 3.0 1.3 � eGFR categories 1.73m 2 ) 45-59 1.2 1.5 1.9 3.4 2.0 � Albuminuria (ACR categories) 30-44 1.7 2.1 3.0 4.4 4.0 15-29 4.0 3.0 4.2 6.0 3.6 � Outcome: mortality risk 1.0 1.3 2.0 3.6 All *P<0.05 CKD by low GFR CKD Prognosis Consortium. Lancet: 2073-81. 2010 3
8/7/2013 Q3: What is the current definition of Outline Stage 3 CKD? � Definition and Complications 1+ proteinuria or ACR > 30 a) � New CKD Staging 2013 59% GFR 30-60 b) GFR 45-60 � Screening for CKD c) There’s no such thing d) � Treatment of CKD 19% 19% � Introduction to Cystatin C 3% � When to refer to nephrologist 0 0 . . . . . 6 6 . a - - c i 0 5 u r 3 4 u s n R R o i F F n e G G t s o ’ e r r p e + h 1 T CKD Stages and Prevalence Problems with Old Staging U.S. Prevalence � Stages 1 and 2 were the same Estimated GFR CKD Stage N (1000’s) (mL/min per 1.73 m 2 ) (%) � Stage 3 (30-60) was too broad; eGFR of 30-45 is CKD Stage 1 90+* 3,200 (1.6) very different from 45-60 CKD Stage 2 60-89* 6,500 (3.2) � Did not address levels of albuminuria; and only used albuminuria for Stages 1 and 2 CKD Stage 3 30–59 15,500 (7.7) CKD Stage 4 15–29 700 (0.4) CKD Stage 5 <15 (or dialysis) 400 (0.2) * With evidence of kidney damage, e.g. albuminuria KDOQI Guidelines, AJKD, Feb. 2002 4
8/7/2013 From Old to New Staging Classification of CKD � It is recommended that CKD be classified by: CGA Staging (like TMN) replaces the prior 5 stages of CKD U.S. Prevalence • “CKD” is an inadequate Estimated GFR � Cause GFR CKD Stage N (1000’s) Cause Albuminuria (mL/min per 1.73 m 2 ) (mL/min per 1.73 m 2 ) (%) � GFR category descriptor (like diabetes) • Define C, G, A whenever you � Albuminuria category CKD Stage 1 90+* 3,200 (1.6) Diabetes G1 (>90) A1 (ACR< 30) mention CKD Hypertension G2 (60-89) • Hypertensive with eGFR= 50, A2 (ACR 30-300) � This is collectively referred to as “CGA Staging” CKD Stage 2 60-89* 6,500 (3.2) Polycystic Disease G3a (45 ACR= 10 -59) A3 (ACR > 300) � Represents a revision of the previous KDOQI CKD CKD Stage 3 30–59 • Diabetic CKD with eGFR= 75, 15,500 (7.7) GN G3b (30 -44) guidelines, which included staging only by level of ACR= 500 Unknown CKD Stage 4 G4 (15 15–29 -29) 700 (0.4) GFR G5 (< 15) CKD Stage 5 <15 (or dialysis) 400 (0.2) Outline Screening for CKD � Definition and Complications � CKD guidelines do not address when or how to screen � New CKD Staging 2013 � Other guidelines have disease-specific � Screening for CKD recommendations (hypertension, diabetes, CVD) � Treatment of CKD � The following are my suggestions. � Introduction to Cystatin C � When to refer to nephrologist 5
8/7/2013 Who and When to Check Creatinine? GFR Estimation from Creatinine � Estimated GFR: � Begin screening: � Automatic reporting by most labs � Age >40 lower-risk populations � Equations are rough � Age >30 Blacks, Native Americans � <60 concerning for kidney disease, but not diagnostic of � Diagnosis of hypertension, diabetes, cardiovascular kidney disease disease, heart failure � > 60- imprecise � 3 equations in current use: � Frequency of creatinine monitoring (no evidence) � Cockroft-Gault (Nephron, 1976)- used by FDA and � No risk factors: 3-5 years pharmacies � Risk factors: 1-2 years � MDRD (Annals, 1999)- used for most automated reporting � Creatinine cost: $0.20 � CKD-EPI (Annals, 2009)- favored by researchers Question 4: Which of the following is Pros and Cons of Estimated GFR true about creatinine GFR estimates? � Pros: More accurate in older populations than middle- a) aged because prevalence of kidney disease is � Indexes creatinine for demographic characteristics higher � Forces us to think in terms of GFR and kidney function They have been validated in most ethnic groups � Cons: b) They are more likely to be accurate in healthy � Mostly validated in younger patients with kidney c) 62% persons than in persons with chronic illness disease � Huge assumption that demographic characteristics All of the above d) alone can define muscle mass 20% 16% � Only developed in Whites and Blacks 2% � Estimated GFR ≠ GFR . . . . . . . . . . . . e n e o t e r b a e o a b m u r e e h c e c v r t a a a f h o e y r y e l l o e h A M h T T 6
8/7/2013 Who to Screen with Urine Albumin? How to Measure Urine Albumin � Primary prevention screens: � Often listed as “microalbumin panel” � Diabetes- annual � Focus on albumin/creatinine ratio (ACR): � Hypertension ACR (mg/g) OLD NEW � Elderly < 30 Normal Normal or mildly elevated � CKD Staging: 30-300 Microalbuminuria Moderately elevated � Urine albumin will be important part of CKD staging � Should be measured and documented in all CKD >300 Macroalbuminuria Severely elevated patients � Dipstick: “trace” is abnormal � Repeat annually in diabetics � every 2-3 years in non-diabetics � If dipstick is abnormal, quantify ACR Question 5: Which of the following treatment options will Outline not slow the progression of kidney disease? � Definition and Complications A. ACE/ARB treatments � New CKD Staging 2013 B. Blood pressure control 79% � Screening for CKD C. Glucose control D. Statins � Treatment of CKD � Introduction to Cystatin C 13% � When to refer to nephrologist 6% 2% ACE/ARB treatm... Blood pressure... Statins Glucose contro... 7
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