Original Investigation
Pathogenesis and Treatment of Kidney Disease
Modification of the Modification of Diet in Renal Disease (MDRD) Study Equation for Japan

https://doi.org/10.1053/j.ajkd.2007.09.004Get rights and content

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.

Section snippets

Methods

We followed 5 steps to obtain an equation that accurately estimates GFR for Japanese patients with CKD.

Creatinine Calibration

Results of creatinine calibration in the 3 laboratories are shown in Table 1 and Fig 1. For 40 reference samples of the calibration panel, values obtained by means of enzymatic methods in the central and TWMU laboratories highly correlated with values assigned by the Cleveland Clinic based on nonsignificant laboratory-specific linear regression intercepts and slopes close to 1. Creatinine values for the central laboratory and TWMU laboratory were not adjusted, although the regression slope for

Discussion

The goal of the study is to establish an equation of accurate GFR estimation for Japanese patients with CKD. Applying the JSN-CKDI coefficient, the modified IDMS MDRD Study equation improved GFR estimation in patients with CKD. The JSN-CKDI equation also provided significantly more accurate GFRs than the original 4-variable IDMS MDRD Study equation. At present, we propose that the modified IDMS MDRD Study equation using the JSN-CKDI coefficient (equation 1) and the JSN-CKDI equation (equation

Acknowledgements

We thank Dr Lesley A. Stevens for critical reading of the manuscript and kind efforts in coordinating the exchange of samples with Dr Van Lente’s laboratory and Drs Shigeko Hara, Toshiki Moriyama, Yasuhiro Ando, Hideki Hirakata, Tsuyoshi Watanabe, Kenji Wakai, Ichiei Narita, Yutaka Kiyohara, and Yoshinari Yasuda for helpful discussions. Fuji Yakuhin Co Ltd provided data from the Cin clinical trial.

Support: None.

Financial Disclosure: None.

References (16)

  • A.S. Levey et al.

    Definition and classification of chronic kidney disease: A position statement from Kidney Disease: Improving Global Outcomes (KDIGO)

    Kidney Int

    (2005)
  • L. Zuo et al.

    Application of GFR-estimating equations in Chinese patients with chronic kidney disease

    Am J Kidney Dis

    (2005)
  • L. Wesson

    Renal hemodynamics in physiologic state, in Physiology of the Human Kidney

  • G.L. Mayers et al.

    Recommendations for improving serum creatinine measurement: A report from the Laboratory Working Group of the National Kidney Disease Education Program

    Clin Chem

    (2006)
  • L.A. Stevens et al.

    Assessing kidney function—Measured and estimated glomerular filtration rate

    N Engl J Med

    (2006)
  • E. Imai et al.

    Estimation of glomerular filtration rate by the MDRD Study equation modified for Japanese patients with chronic kidney disease

    Clin Exp Nephrol

    (2007)
  • Y.C. Ma et al.

    Modified glomerular filtration rate estimating equation for Chinese patients with chronic kidney disease

    J Am Soc Nephrol

    (2006)
  • A.S. Levey et al.

    Using standardized serum creatinine values in the Modification of Diet in Renal Disease Study equation for estimating glomerular filtration rate

    Ann Intern Med

    (2006)
There are more references available in the full text version of this article.

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