Impact of Creatinine Calibration on Performance of GFR Estimating Equations in a Pooled Individual Patient Database

Lesley A. Stevens, Jane Manzi, Andrew S. Levey, Jing Chen, Amy E. Deysher, Tom Greene, Emilio D. Poggio, Christopher H. Schmid, Michael W. Steffes, Yaping (Lucy) Zhang, Frederick Van Lente, Josef Coresh

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187 Scopus citations


Background: Variation in performance of glomerular filtration rate (GFR) estimating equations is related to variation in calibration of the creatinine assay across clinical laboratories. Study Design: Cross-sectional analysis. Setting & Participants: 6 research studies and 4 clinical populations including 5,504 participants who had GFR measured using urinary clearance of iothalamate. Measurements: Standardized serum creatinine values obtained by means of calibration to the Cleveland Clinic Research Laboratory using frozen specimens, a calibration panel, and/or survey results from the College of American Pathologists. Predictor: Noncalibrated serum creatinine assayed in research and clinical laboratories compared with standardized serum creatinine. Outcome: Difference between measured GFR versus GFR estimated from the Modification of Diet in Renal Disease (MDRD) Study and Cockcroft-Gault equations. Results: For a noncalibrated serum creatinine value of 1 mg/dL (88.4 μmol/L), standardized serum creatinine value was 0.07 mg/dL (6.2 μmol/L) less than noncalibrated values. In the pooled data set, for the MDRD Study equation, calibration improved median percentage of difference between measured and estimated GFR from 9.0% (interquartile range [IQR], 28%) to 5.8% (IQR, 28%) and improved the percentage of estimates within 30% of measured GFR (P30) from 80% to 83%. The effect of calibration was greater at higher levels of GFR and varied across studies. For the Cockcroft-Gault equation, calibration worsened the median percentage of difference from -2.0% (IQR, 38%) to -11.4% (IQR, 39%), and the P30, from 74% to 69%. Limitations: College of American Pathologist samples were used for calibration of clinical populations; calibration factors do not account for drift over time in the serum creatinine assay; calibration cannot account for variation in assay performance among individuals. Conclusion: Calibration improves the performance of the MDRD Study equation. After calibration, larger errors remain for GFR estimates greater than 60 mL/min/1.73 m2 (>1 mL/s/1.73 m2).

Original languageEnglish (US)
Pages (from-to)21-35
Number of pages15
JournalAmerican Journal of Kidney Diseases
Issue number1
StatePublished - Jul 2007

Bibliographical note

Funding Information:
CKD-EPI is funded by grants from the National Institute of Diabetes, Digestive, and Kidney Disease (NIDDK) as part of a cooperative agreement in which the NIDDK has substantial involvement in the design of the study and collection, analysis, and interpretation of the data. The NIDDK was not required to approve publication of the finished manuscript. The institutional review boards of all participating institutions approved the study.


  • Chronic kidney disease
  • Cockcroft-Gault equation
  • Modification of Diet in Renal Disease Study equation
  • calibration
  • creatinine
  • estimated glomerular filtration rate
  • glomerular filtration rate
  • individual patient meta-analysis


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