Original Investigation
Pathogenesis and Treatment of Kidney Disease
Calibration of Serum Creatinine in the National Health and Nutrition Examination Surveys (NHANES) 1988-1994, 1999-2004

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Background

The calibration of serum creatinine values to standardized creatinine and the commutability of serum creatinine across surveys are essential to the correct use of National Health and Nutrition Examination Survey (NHANES) data for kidney function and for generating estimates of the burden of kidney disease in the United States.

Study Design

Calibration study of serum creatinine in NHANES III (1988-1994) and NHANES 1999-2000, 2001-2002, and 2003-2004 to directly compare creatinine measurements from the original surveys with standard creatinine measured using an assay traceable to known gold-standard methods. We also assessed predictors of differences between methods (potential interferences) in this general population.

Setting & Participants

The NHANES are ongoing cross-sectional surveys of the civilian noninstitutionalized population of the United States. We selected random samples of approximately 200 stored specimens from persons aged 60 years or older from each survey (NHANES III, 1999-2000, 2001-2002, and 2003-2004).

Measurements

Stored serum specimens from the 4 NHANES surveys were analyzed for serum creatinine by using a Roche enzymatic assay implemented at the Cleveland Clinic Research Laboratory (CCRL). The Roche assay is traceable to gold-standard reference methods. The original NHANES serum creatinine values were obtained using the Jaffé method (kinetic alkaline picrate) implemented in several different laboratories.

Results

Overall agreement between the original NHANES values (Jaffé method) and CCRL measurements (Roche enzymatic) was high, but substantial biases were observed in NHANES III and 1999-2000. No bias was observed in NHANES 2001-2002 and 2003-2004. Final calibration equations to correct serum creatinine values in the relevant surveys are provided. Assay differences were independent of sex, race/ethnicity, and bilirubin and triglyceride levels, but weakly related to age and glucose concentration.

Limitations

We were not able to examine drift in measurements over time within each survey or directly evaluate freeze-thaw effects.

Conclusions

The magnitude of differences in serum creatinine measurements in NHANES III and 1999-2000 from standard creatinine would result in large differences in estimates of kidney function (10% to 20%). Thus, correction of original creatinine values in NHANES III and 1999-2000 is essential, but no correction is needed for NHANES 2001-2002 or 2003-2004.

Section snippets

NHANES

The NHANES are ongoing cross-sectional surveys of the civilian noninstitutionalized population of the United States. These surveys are conducted by the National Center for Health Statistics (NCHS) and designed to assess the health and nutritional status of adults and children in the United States. Detailed in-person interviews, physical examinations, and serum samples are obtained from thousands of participants in each survey.4, 5

The original serum creatinine assays in the NHANES III

Results

Of 800 sampled specimens, 781 were available in sufficient quantities for measurement. We further excluded 11 outliers from the analyses by using our prespecified criteria. The final sample sizes by survey were 190 in NHANES III, 196 in 1999-2000, 194 in 2001-2002, and 190 in 2003-2004.

Overall agreement between the original NHANES serum creatinine measurements and measurements done by CCRL using the Roche enzymatic method was high, indicated by Pearson correlation coefficients (Table 1). Mean

Discussion

The magnitude of the difference in serum creatinine measurements in NHANES III and 1999-2000 from gold-standard methods would result in large differences in estimates of GFR regardless of the estimating equation used. Thus, correction of original serum creatinine values for NHANES III and 1999-2000 is essential for the appropriate estimation of kidney function in these studies.

We previously directly compared serum creatinine measurements from NHANES III performed at the Coulston Laboratory with

Acknowledgements

The authors thank Dr Geraldine McQuillan (NCHS) for assistance.

Support: This work was supported by grants from the National Institutes of Health and the National Institute of Diabetes and Digestive and Kidney Diseases (K01 DK076595 to Dr Selvin, UO1 DK 053869 to Dr Levey, UO1 DK 067651 and R21DK67651 to Dr Coresh). Dr Coresh was also supported by the National Center for Research Resources (GCRC grant RR00722).

Financial Disclosure: None.

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Originally published online as doi:10.1053/j.ajkd.2007.08.020 on November 5, 2007.

Because an author of this manuscript is an editor for AJKD, the peer-review and decision-making processes were handled entirely by an outside editor, Bryan Becker, MD, University of Wisconsin, who served as Acting Editor-in-Chief. Details of the journal’s procedures for potential editor conflicts are given in the Editorial Policies section of the AJKD website.

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