A New Panel-Estimated GFR, Including β2-Microglobulin and β-Trace Protein and Not Including Race, Developed in a Diverse Population

Abstract

Rationale and objective: Glomerular filtration rate (GFR) estimation based on creatinine and cystatin C (eGFR_cr-cys) is more accurate than estimated GFR (eGFR) based on creatinine or cystatin C alone (eGFR_cr or eGFR_cys, respectively), but the inclusion of creatinine in eGFR_cr-cys requires specification of a person's race. β₂-Microglobulin (B2M) and β-trace protein (BTP) are alternative filtration markers that appear to be less influenced by race than creatinine is.

Study design: Study of diagnostic test accuracy.

Setting and participants: Development in a pooled population of 7 studies with 5,017 participants with and without chronic kidney disease. External validation in a pooled population of 7 other studies with 2,245 participants.

Tests compared: Panel eGFR using B2M and BTP in addition to cystatin C (3-marker panel) or creatinine and cystatin C (4-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 [⁵¹Cr]EDTA.

Results: Mean measured GFRs were 58.1 and 83.2 mL/min/1.73 m², and the proportions of Black participants were 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 with equations without age and sex, but addition of race did not further improve the performance. In validation, the 4-marker panels were more accurate than the 3-marker panels (P < 0.001). The 3-marker panel without race was more accurate than eGFR_cys (percentage of estimates greater than 30% different from measured GFR [1 - P₃₀] of 15.6% vs 17.4%; P = 0.01), and the 4-marker panel without race was as accurate as eGFR_cr-cys (1 - P₃₀ of 8.6% vs 9.4%; P = 0.2). 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 4-marker panel eGFR is as accurate as eGFR_cr-cys without requiring specification of race. A more accurate race-free eGFR could be an important advance.

Keywords: African American; Black race; GFR estimation; Glomerular filtration rate (GFR); bias; creatinine; cystatin C; estimating equations; filtration marker; kidney disease diagnosis; laboratory testing; race; race-based medicine; renal function; β(2)-microglobulin (B2M); β-trace protein (BTP).

Figure 1:. Performance of Reference eGFR and Panel eGFR Equations in the External Validation Population and Overall and by Race

Accuracy as measured by 1- P₃₀ or the percentage of estimates greater than 30% of measured GFR. The vertical bars indicate 95% confidence intervals. Solid lines indicate equations that include creatinine. Purple indicates the 2009 CKD-EPI creatinine equation; Orange indicates the 2012 CKD-EPI cystatin C and creatinine-cystatin C equations; Green indicates the new 2020 CKD-EPI three and four marker panels.