RATIONALE AND OBJECTIVE: GFR estimation based on creatinine and cystatin C (eGFRcr-cys) is more accurate than eGFR based on either creatinine or cystatin C alone (eGFRcr or eGFRcys), but the inclusion of creatinine in eGFRcr-cys requires specification of a person's race. Beta-2-microglobulin (B2M) and beta-trace protein (BTP) are alternative filtration markers that appear to be less influenced by race than creatinine.

STUDY DESIGN: Study of diagnostic test accuracy.

SETTING: and Participants: Development in pooled population of seven studies with 5017 participants with and without chronic kidney disease. External validation in a pooled population of seven other studies with 2245 participants.

TESTS COMPARED: Panel eGFR using B2M and BTP in addition to cystatin C (three-marker panel) or creatinine and cystatin C (four-marker panel) with and without age and sex or race.

OUTCOMES: GFR measured as the urinary clearance of iothalamate, plasma clearance of iohexol, or plasma clearance of Cr-EDTA RESULTS: Mean measured GFR was 58.1 and 83.2 ml/min/1.73m2 and the proportion of blacks was 38.6% and 24.0%, in the development and validation populations, respectively. In development, addition of age and sex improved the performance of all equations compared to equations without age and sex, but addition of race did not further improve the performance. In validation, the four-marker panels were more accurate than the three-marker panels (p<0.001). The three-marker panel without race was more accurate than eGFRcys [1- P30 of 15.6 vs 17.4% (p=0.014)], and the four-marker panel without race was as accurate as eGFRcr-cys [1- P30 of 8.6 vs 9.4% (p=0.17)]. Results were generally consistent across subgroups.

LIMITATIONS: No representation of participants with severe comorbid illness and from geographic areas outside of North America and Europe.

CONCLUSIONS: The four-marker panel eGFR is as accurate as eGFRcr-cys, without requiring specification of race. A more accurate race-free eGFR could be an important advance.