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Section 2: Detection of CKD
What Tests Are Available?
• Direct GFR measurement
Accurate
– Inulin clearance
– Radionuclides
– Iohexol clearance
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3 hr CrCl with Cimetidine
Prediction equations
Cystatin C
24 hr urine CrCl
Serum creatinine
Inaccurate
Gold Standards
• Inulin clearance
– 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
Serum creatinine (µmol/L)
600
400
200
5 4
3
2
CKD stage
Proportion
misdiagnosis
0
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
220
Males
200
180
sCr (µmol/L)
180
sCr (µmol/L)
Females
200
160
79.4%
140
120
160
98.4%
140
120
27.7%
81%
100
100
80
80
30
40
50
60
2
eGFR (ml/min/1.73m )
30
40
50
60
2
eGFR (ml/min/1.73m )
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
Normal
Microalbuminuria
Macroalbuminuria
(clinical proteinuria)
uACR
(mg/mmol)
uPCR
(mg/mmol)
Dipstick
<2.5 (males)
< 3.5 (females)
<15
-
< 2.5-30 (males)
< 3.5-30 (females)
15-44
-/trace
>30
45-449
+/++
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
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
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Stage 1:
Stage 2:
Stage 3A:
Stage 3B:
Stage 4:
Stage 5:
GFR>90 + abnormal urinalysis
GFR 60-89 + abnormal urinalysis
GFR 45-59
GFR 30-44
GFR 15-29
GFR <15 or dialysis dependent
Suffix P denotes presence of proteinuria (ACR>30
or PCR>50)