Estimating GFR using serum cystatin C alone and in combination with serum creatinine: a pooled analysis of 3,418 individuals with CKD.
BACKGROUND
Serum cystatin C was proposed as a potential replacement for serum creatinine in glomerular filtration rate (GFR) estimation. We report the development and evaluation of GFR-estimating equations using serum cystatin C alone and serum cystatin C, serum creatinine, or both with demographic variables.


METHODS
Test of diagnostic accuracy.


METHODS
Participants screened for 3 chronic kidney disease (CKD) studies in the United States (n = 2,980) and a clinical population in Paris, France (n = 438).


METHODS
Measured GFR (mGFR).


METHODS
Estimated GFR using the 4 new equations based on serum cystatin C alone, serum cystatin C, serum creatinine, or both with age, sex, and race. New equations were developed by using linear regression with log GFR as the outcome in two thirds of data from US studies. Internal validation was performed in the remaining one third of data from US CKD studies; external validation was performed in the Paris study.


METHODS
GFR was measured by using urinary clearance of iodine-125-iothalamate in the US studies and chromium-51-EDTA in the Paris study. Serum cystatin C was measured by using Dade-Behring assay, standardized serum creatinine values were used.


RESULTS
Mean mGFR, serum creatinine, and serum cystatin C values were 48 mL/min/1.73 m(2) (5th to 95th percentile, 15 to 95), 2.1 mg/dL, and 1.8 mg/L, respectively. For the new equations, coefficients for age, sex, and race were significant in the equation with serum cystatin C, but 2- to 4-fold smaller than in the equation with serum creatinine. Measures of performance in new equations were consistent across the development and internal and external validation data sets. Percentages of estimated GFR within 30% of mGFR for equations based on serum cystatin C alone, serum cystatin C, serum creatinine, or both levels with age, sex, and race were 81%, 83%, 85%, and 89%, respectively. The equation using serum cystatin C level alone yields estimates with small biases in age, sex, and race subgroups, which are improved in equations including these variables.


CONCLUSIONS
Study population composed mainly of patients with CKD.


CONCLUSIONS
Serum cystatin C level alone provides GFR estimates that are nearly as accurate as serum creatinine level adjusted for age, sex, and race, thus providing an alternative GFR estimate that is not linked to muscle mass. An equation including serum cystatin C level in combination with serum creatinine level, age, sex, and race provides the most accurate estimates.
Stevens
Lesley A
LA
Division of Nephrology, Tufts-New England Medical Center, 750 Washington St, Box #391, Boston, MA 02111, USA. lstevens1@tufts-nemc.org
Coresh
Josef
J
Schmid
Christopher H
CH
Feldman
Harold I
HI
Froissart
Marc
M
Kusek
John
J
Rossert
Jerome
J
Van Lente
Frederick
F
Bruce
Robert D
RD
Zhang
Yaping Lucy
YL
Greene
Tom
T
Levey
Andrew S
AS
D000328:Adult; D015415:Biomarkers / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology; D015897:Comorbidity; D003404:Creatinine / Q000097:blood*; D055316:Cystatin C; D015891:Cystatins / Q000097:blood*; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006801:Humans; D007677:Kidney Function Tests / Q000379:methods*; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000453:epidemiology / Q000503:physiopathology*
D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D003404:Creatinine