title: Estimating GFR using serum cystatin C alone and in combination with serum creatinine: a pooled analysis of 3,418 individuals with CKD.
abstract: 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.
authors.affiliation: Division of Nephrology, Tufts-New England Medical Center, 750 Washington St, Box #391, Boston, MA 02111, USA. lstevens1@tufts-nemc.org
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Stevens
authors.forename: Josef
authors.initials: J
authors.lastname: Coresh
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Schmid
authors.forename: Harold I
authors.initials: HI
authors.lastname: Feldman
authors.forename: Marc
authors.initials: M
authors.lastname: Froissart
authors.forename: John
authors.initials: J
authors.lastname: Kusek
authors.forename: Jerome
authors.initials: J
authors.lastname: Rossert
authors.forename: Frederick
authors.initials: F
authors.lastname: Van Lente
authors.forename: Robert D
authors.initials: RD
authors.lastname: Bruce
authors.forename: Yaping Lucy
authors.initials: YL
authors.lastname: Zhang
authors.forename: Tom
authors.initials: T
authors.lastname: Greene
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Levey
mesh_terms: 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*
chemical_list: D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D003404:Creatinine