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– 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 amputeesAnalytical problems• Non-specificity (protein, ketones, ascorbic acid)• No international standardization• Spectral interferences (icterus/lipaemia/haemolysis)

Serum CreatinineHides Early Renal Damage

Se

rum

cre

atin

ine

(µ

mo

l/L)

GFR (mL/min/1.73m2)35 70 105 140

600

400

200

0

2345 CKD stage

Reproduction from the late David Newman

Proportionmisdiagnosis

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 formulaCockcroft-Gault formula

Ccr (ml/min) = 1.23 x (140-age) x weight/Pcr

(x 0.85 if female)

MDRD Study equationMDRD 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. Cockcroft & Gault. NephronNephron 1976;1976; 16: 31-41 16: 31-41 Levey AS, et al. Levey AS, et al. Ann Intern MedAnn Intern Med 1999;130: 461-70 1999;130: 461-70

MDRD equation vs serum creatinine

30 40 50 60

220

200

180

160

140

120

100

8030 40 50 60

Males Females

eGFR (ml/min/1.73m2)

Middleton et al 2004

eGFR (ml/min/1.73m2)

sCr

(µm

ol/L

)

220

200

180

160

140

120

100

80

sCr

(µm

ol/L

)

79.4%

27.7%

98.4%

81%

Scatter Increases as GFR Approaches Physiological Levels

Froissart et al JASN 2005;16:763-773Froissart 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 (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)

>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) 20026. 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 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)