section 2: detection of ckd. what tests are available? direct gfr measurement –inulin clearance...
TRANSCRIPT
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)