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 – 125 Iodine-iothalamate, technetium DTPA, 51 Chromium-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. Serum Creatinine Hides Early Renal Damage Serum creatinine (µmol/L) GFR (mL/min/1.73m 2 ) 3570105140 600 400 200 0 234 5 CKD stage Reproduction from the late David Newman Proportion misdiagnosis

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 C cr (ml/min) = 1.23 x (140-age) x weight/P cr (x 0.85 if female) MDRD Study equation GFR (ml/min/1.73 m 2 ) = 186 x [(P cr )/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

8. MDRD equation vs serum creatinine 30405060 220 200 180 160 140 120 100 80 30405060 Males Females eGFR (ml/min/1.73m 2 ) Middleton et al 2004 eGFR (ml/min/1.73m 2 ) sCr (µmol/L) 220 200 180 160 140 120 100 80 sCr (µmol/L) 79.4% 27.7% 98.4% 81%

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’ population 1,2 –12-30% of the hypertensive population 1,3,4 –25%-40% of people with diabetes 1,5 Comparison of tests uACR (mg/mmol) uPCR (mg/mmol) Dipstick Normal <2.5 (males) < 3.5 (females) <15- Microalbuminuria < 2.5-30 (males) < 3.5-30 (females) 15-44-/trace Macroalbuminuria (clinical proteinuria) >3045-449+/++ 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 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)