Modification of the Modification of Diet in Renal Disease (MDRD) Study Equation for Japan

Background

Glomerular filtration rate (GFR)-estimating equations based on serum creatinine level may not be accurate across racial groups because of differences among races in creatinine generation. The Modification of Diet in Renal Disease (MDRD) Study equation was developed in whites and African Americans, but performance was not evaluated in Japanese.

Study Design

Diagnostic test accuracy. Cross-sectional retrospective study of 3 patient groups. Equation development in 2 groups (n = 247 in 2002 to 2004; n = 214 in 2003 to 2004 with measured GFR <90 mL/min/1.73 m²); external validation in a separate group (n = 153 from 1988 to 1994).

Setting & Participants

Hospitalized Japanese patients with chronic kidney disease in 3 medical centers.

Reference Test

Measured GFR (mGFR) computed from renal clearance of inulin.

Index Test

Estimated GFR (eGFR) using the isotope dilution mass spectrometry (IDMS)-traceable 4-variable MDRD Study equation, a modified IDMS MDRD Study equation with a Japanese Society of Nephrology-Chronic Kidney Disease Initiatives (JSN-CKDI) coefficient derived in the development data set, and a new equation derived by refitting coefficients in the MDRD Study equation in the development data set.

Measurements

Current creatinine assays were calibrated to standardized creatinine. Performance of equations was assessed as bias, accuracy, root-mean-squared error, and correlation coefficient of eGFR versus mGFR.

Results

In the development data set, eGFR using the IDMS MDRD Study equation overestimated mGFR throughout the entire range. In the validation data set, the IDMS MDRD Study equation with the JSN-CKDI coefficient 0.741 and the new equation (JSN-CKDI) performed with significantly less bias and greater accuracy than the IDMS MDRD Study equation, but were similar to each other in accuracy and bias in patients with eGFR less than 60 mL/min/1.73 m². In the combined development and validation data sets, the JSN-CKDI coefficient was 0.763 (95% confidence interval, 0.743 to 0.783).

Limitations

Possible drift in creatinine assays over time, possible lower creatinine generation in hospitalized patients, exclusion of patients with higher GFR from the development data set.

Conclusion

GFR estimates using the IDMS MDRD Study equation with the JSN-CKDI coefficient or the new JSN-CKDI equation are more accurate than the IDMS MDRD Study equation in hospitalized Japanese patients with eGFR less than 60 mL/min/1.73 m². More studies are necessary to verify the accuracy of the JSN-CKDI coefficient and JSN-CKDI equation in other settings in Japan and elsewhere in Asia.

Index Words: Creatinine, glomerular filtration rate, Modification of Diet in Renal Disease Study, inulin clearance