Original Investigations: Pathogenesis and Treatment
Calibration and random variation of the serum creatinine assay as critical elements of using equations to estimate glomerular filtration rate,☆☆,

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Abstract

Equations using serum creatinine level, age, sex, and other patient characteristics often are used to estimate glomerular filtration rate (GFR) in both clinical practice and research studies. However, the critical dependence of these equations on serum creatinine assay calibration often is overlooked, and the reproducibility of estimated GFR is rarely discussed. We address these issues in frozen samples from 212 Modification of Diet in Renal Disease (MDRD) study participants and 342 Third National Health and Nutrition Examination Survey (NHANES III) participants assayed for serum creatinine level a second time during November 2000. Variation in serum creatinine level was assessed in 1,919 NHANES III participants who had serum creatinine measured on two visits a median of 17 days apart. Linear regression was used to compare estimates. Calibration of serum creatinine varied substantially across laboratories and time. Data indicate that serum creatinine assays on the same samples were 0.23 mg/dL higher in the NHANES III than MDRD study. Data from the College of American Pathologists suggest that a difference of this magnitude across laboratories is not unusual. Conversely, serum creatinine assays an average of 2 weeks apart have better precision (SD of percentage of difference in estimated GFR, 15%; 90% of estimates within 21%). Errors in calibration make little difference in estimating severely decreased GFR (<30 mL/min/1.73 m2), but result in progressively larger differences at higher GFRs. Both clinical and research use of serum creatinine or equations to estimate GFR require knowledge of the calibration of the serum creatinine assay. © 2002 by the National Kidney Foundation, Inc.

Section snippets

Methods

Serum creatinine was measured as part of both the MDRD study (1989 to 1991) and NHANES III (1988 to 1994). Both studies were funded by The National Institutes of Health and reported good quality control, providing an opportunity to show the issues in applying an equation developed for estimating GFR based on serum creatinine assays in one laboratory to serum creatinine assays obtained in another laboratory. Repeated analysis of frozen serum from both studies allows for examination of

Results

Figure 1 shows the comparison of original serum creatinine measurements in the MDRD study to duplicate measurements on thawed samples in the Cleveland Clinic and White Sands laboratories during 2000.

. Scatter plot of serum creatinine (sCr) values assayed in 2,000 (new) in the (A) Cleveland Clinic and (B) White Sands laboratories compared with values measured during the MDRD study (old). Outliers, defined as values in which any pair of serum creatinine measurements differs by 1 mg/dL or more, are

Discussion

Given appropriate calibration of the serum creatinine assay, estimates of GFR can be reproducible (SD of estimates 2 weeks apart, 15%). For example, at moderately decreased GFRs (GFR, 30 to 59 mL/min/1.73 m2), estimates of GFR based on serum creatinine level are precise enough to allow for diagnosis and clinical management. At this GFR range, a follow-up estimated GFR will be within 27% and a measured iothalamate GFR will be within 30% of the original estimate most of the time, corresponding to

Acknowledgements

The authors thank the White Sands and Cleveland Clinic laboratories, which facilitated the conduct of this study by conducting assays and providing access to their quality control data; investigators and participants of the MDRD study and NHANES III, which provided data for this study; as well as their funding institutes, the National Institute of Diabetes, Digestive and Kidney Disease and the National Center for Health Statistics.

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Supported in part by a grant from the National Kidney Foundation as part of the Kidney Disease Outcomes Quality Initiative; and National Institutes of Health grants no. DK48362 and RR00722 (J.C.); grant no. UO1 DK35073 (T.G.); grants no. RO1 DK53869 and UO1 DK35073 (A.S.L.); and grant no. T32HL7024 (B.C.A.).

☆☆

Address reprint requests to Josef Coresh, MD, PhD, 2024 E Monument, Baltimore, MD 21205. E-mail: [email protected]

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