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Section 2: Detection of CKD

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

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Section 2: Detection of CKD

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  1. Section 2: Detection of CKD

  2. 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

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

  4. 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)

  5. 4 3 2 CKD stage 5 35 70 105 140 Serum CreatinineHides Early Renal Damage 600 400 Serum creatinine (µmol/L) 200 Proportion misdiagnosis 0 GFR (mL/min/1.73m2) Reproduction from the late David Newman

  6. 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

  7. 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. Nephron1976;16: 31-41 Levey AS, et al. Ann Intern Med 1999;130: 461-70

  8. MDRD equation vs serum creatinine 220 200 180 160 140 120 100 80 220 200 180 160 140 120 100 80 Females Males sCr (µmol/L) 79.4% 98.4% sCr (µmol/L) 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

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

  10. MDRD Formula: validation

  11. 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 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

  12. 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’

  13. NICE: 2008 Classification of CKDwaking 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)

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