Section 2: Detection of CKD

What Tests Are Available? Direct GFR measurement Inulin clearance Radionuclides Iohexol clearance 3 hr CrCl with Cimetidine Prediction equations Cystatin C 24 hr urine CrCl Serum creatinine Accurate Inaccurate

Gold Standards Inulin clearance Radionuclides Tedious, time consuming & unavailable Radionuclides 125Iodine-iothalamate, technetium DTPA, 51Chromium-EDTA clearance Time consuming and expensive Research, accurate drug dosing

Serum Creatinine: Problems Non-renal influences Gender, ethnicity, age and muscle mass Nutrition/diet Drugs (e.g. cimetidine) Clinical utility Poor sensitivity for CKD Not useful in ARF Muscle wasting disorders and amputees Analytical problems Non-specificity (protein, ketones, ascorbic acid) No international standardization Spectral interferences (icterus/lipaemia/haemolysis)

Serum Creatinine Hides Early Renal Damage 600 400 Serum creatinine (µmol/L) 200 2 3 4 5 CKD stage Proportion misdiagnosis 35 70 105 140 GFR (mL/min/1.73m2) Reproduction from the late David Newman

Glomerular Filtration Rate Sum of all nephron filtration rates Best index of overall function Reduction implies a problem Translatable concept Equates to percentage Kidney function

GFR Prediction Equations Cockcroft-Gault formula Ccr (ml/min) = 1.23 x (140-age) x weight/Pcr (x 0.85 if female) MDRD Study equation GFR (ml/min/1.73 m2) = 186 x [(Pcr)/88.4]-1.154 x (age)-0.203 x (0.742 if female) x (1.210 if African American) Cockcroft & Gault. Nephron 1976; 16: 31-41 Levey AS, et al. Ann Intern Med 1999;130: 461-70

MDRD equation vs serum creatinine 220 200 180 160 140 120 100 80 220 200 180 160 140 120 100 80 Males Females sCr (µmol/L) 79.4% sCr (µmol/L) 98.4% 27.7% 81% 30 40 50 60 30 40 50 60 eGFR (ml/min/1.73m2) eGFR (ml/min/1.73m2) Middleton et al 2004

Scatter Increases as GFR Approaches Physiological Levels Froissart et al JASN 2005;16:763-773

MDRD Formula: validation

What is Microalbuminuria? Definitions and prevalence Microalbuminuria is found in: 5-7% of the ‘healthy’ population1,2 12-30% of the hypertensive population1,3,4 25%-40% of people with diabetes1,5 Comparison of tests uACR (mg/mmol) uPCR Dipstick Normal <2.5 (males) < 3.5 (females) <15 - Microalbuminuria < 2.5-30 (males) < 3.5-30 (females) 15-44 -/trace Macroalbuminuria (clinical proteinuria) >30 45-449 +/++ Recent data from large population-based studies like PREVEND1, the National Health and Nutrition Examination Survey (NHANES) III2, the AusDiab Kidney Study3 and the LIFE4 (Losartan Intervention For Endpoint reduction) trial have indicated the prevalence of microalbuminuria in the ‘healthy’, hypertensive and diabetic population which are shown here. The table shows the relationship of the relationship between UACR, UPCR and dipstick results. 1. Hillege et al. J Internal Medicine 2001 249: 519-526 (PREVEND) 2. Garg et al. Kidney International (NHANES-III) 2002 3. Atkins et al. Kidney International Supplement (AUSDIAB) 2004 4. Wachtell et al. Am Heart J. (LIFE) 1.Yuyun et al. Current Opinion in Nephrology and Hypertension 2005;14(3):271-6 2. Hillege et al. J Internal Medicine 2001 249: 519-526 (PREVEND) 3. Garg et al. Kidney International (NHANES-III) 2002 4. Atkins et al. Kidney International Supplement (AUSDIAB) 2004 5. Wachtell et al. Am Heart J. (LIFE) 2002 6. RA/RCP Joint CKD Guidelines 2006

NICE 2008: Diagnosis of CKD Proteinuria=ACR>30 or PCR>50 (NOT dipstick) 3 eGFR estimations <60 over a period not less than 90 days Progressive decline defined as eGFR falling by >5mls/min/year Focus on those whose observed rate of decline would necessitate RRT ‘within their lifetime’

NICE: 2008 Classification of CKD waking up to the impact of proteinuria Stage 1: GFR>90 + abnormal urinalysis Stage 2: GFR 60-89 + abnormal urinalysis Stage 3A: GFR 45-59 Stage 3B: GFR 30-44 Stage 4: GFR 15-29 Stage 5: GFR <15 or dialysis dependent Suffix P denotes presence of proteinuria (ACR>30 or PCR>50)