GFR Estimation Using Standardized Serum Cystatin C in Japan

Background Recently, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) developed glomerular filtration rate (GFR)-estimating equations based on standardized serum cystatin C (CKD-EPIcys) and standardized serum creatinine plus standardized serum cystatin C (CKD-EPIcr-cys). We developed new GFR-estimating equations based on standardized cystatin C for a Japanese population and compared their accuracy with the CKD-EPI equations. Study Design Accuracy of diagnostic test study. Setting & Participants 413 (development data set) and 350 individuals (validation data set). Index Test CKD-EPIcys; CKD-EPIcr-cys; modifications to CKD-EPIcys and CKD-EPIcr-cys using Japanese coefficients; and newly developed Japanese eGFR equations based on standardized serum cystatin C (Eqcys), cystatin C with a nonrenal factor reflecting hypothesized extrarenal elimination (Eqcys+nonrenal), and creatinine in combination with cystatin C (Eqcr-cys). Standardized cystatin C values were determined by a colloidal gold immunoassay traceable to the international certified reference material ERM-DA471/IFCC. Reference Test Measured GFR by inulin renal clearance. Results In a development data set, we calculated Japanese coefficients for CKD-EPIcys and CKD-EPIcr-cys of 0.977 (95% CI, 0.853-1.002) and 0.908 (95% CI, 0.889-0.928), respectively. In a validation data set, we compared CKD-EPIcys, Eqcys, and Eqcys+nonrenal with each other. Bias and accuracy were not significantly different among the 3 equations. The precision of CKD-EPIcys was significantly better than for Eqcys (P = 0.007) and not significantly different from Eqcys+nonrenal (P = 0.6). We then compared 0.908 × CKD-EPIcr-cys, Eqcr-cys, and Eqaverage (the average value of Eqcr [previous Japanese equation based on standardized serum creatinine] and Eqcys+nonrenal) with each other in the validation data set. Bias and accuracy were not significantly different among the 3 equations. The precision of 0.908 × CKD-EPIcr-cys was significantly better than for Eqcr-cys (P = 0.004) and not significantly different from Eqaverage (P = 0.06). Limitations Limited number of participants with measured GFR >90 mL/min/1.73 m2. Extrarenal elimination of cystatin C was not measured. Conclusions CKD-EPIcys performed well in Japanese individuals, suggesting that equations based on serum cystatin C could be used in patients with different races without modification. Accounting for extrarenal elimination of cystatin C may improve the performance of estimating equations. Recently, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) developed glomerular filtration rate (GFR)-estimating equations based on standardized serum cystatin C (CKD-EPIcys) and standardized serum creatinine plus standardized serum cystatin C (CKD-EPIcr-cys). We developed new GFR-estimating equations based on standardized cystatin C for a Japanese population and compared their accuracy with the CKD-EPI equations. Accuracy of diagnostic test study. 413 (development data set) and 350 individuals (validation data set). CKD-EPIcys; CKD-EPIcr-cys; modifications to CKD-EPIcys and CKD-EPIcr-cys using Japanese coefficients; and newly developed Japanese eGFR equations based on standardized serum cystatin C (Eqcys), cystatin C with a nonrenal factor reflecting hypothesized extrarenal elimination (Eqcys+nonrenal), and creatinine in combination with cystatin C (Eqcr-cys). Standardized cystatin C values were determined by a colloidal gold immunoassay traceable to the international certified reference material ERM-DA471/IFCC. Measured GFR by inulin renal clearance. In a development data set, we calculated Japanese coefficients for CKD-EPIcys and CKD-EPIcr-cys of 0.977 (95% CI, 0.853-1.002) and 0.908 (95% CI, 0.889-0.928), respectively. In a validation data set, we compared CKD-EPIcys, Eqcys, and Eqcys+nonrenal with each other. Bias and accuracy were not significantly different among the 3 equations. The precision of CKD-EPIcys was significantly better than for Eqcys (P = 0.007) and not significantly different from Eqcys+nonrenal (P = 0.6). We then compared 0.908 × CKD-EPIcr-cys, Eqcr-cys, and Eqaverage (the average value of Eqcr [previous Japanese equation based on standardized serum creatinine] and Eqcys+nonrenal) with each other in the validation data set. Bias and accuracy were not significantly different among the 3 equations. The precision of 0.908 × CKD-EPIcr-cys was significantly better than for Eqcr-cys (P = 0.004) and not significantly different from Eqaverage (P = 0.06). Limited number of participants with measured GFR >90 mL/min/1.73 m2. Extrarenal elimination of cystatin C was not measured. CKD-EPIcys performed well in Japanese individuals, suggesting that equations based on serum cystatin C could be used in patients with different races without modification. Accounting for extrarenal elimination of cystatin C may improve the performance of estimating equations.