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 Radionuclides
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. 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

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] x (age) 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:

8. 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%
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:

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
Comparison of tests
uACR
(mg/mmol)
uPCR
Dipstick
Normal
<2.5 (males)
< 3.5 (females)
<15 -
Microalbuminuria
< (males)
< (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 : (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 : (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 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)