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American Journal of Kidney Diseases

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

Published:December 07, 2020DOI:https://doi.org/10.1053/j.ajkd.2020.11.005

      Rationale and Objective

      Glomerular filtration rate (GFR) estimation based on creatinine and cystatin C (eGFRcr-cys) is more accurate than estimated GFR (eGFR) based on creatinine or cystatin C alone (eGFRcr or eGFRcys, respectively), but the inclusion of creatinine in eGFRcr-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 eGFRcys (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 eGFRcr-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 eGFRcr-cys without requiring specification of race. A more accurate race-free eGFR could be an important advance.

      Graphical abstract

      Index Words

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      Linked Article

      • Comparing Multiple-Biomarker Panels for Estimating GFR With Estimating Equations Without a Coefficient Distinguishing Black Individuals From Persons of Other Groups
        American Journal of Kidney DiseasesVol. 77Issue 5
        • Preview
          Inker et al1 propose a new estimated glomerular filtration rate (GFR) equation integrating a panel of biomarkers (creatinine, cystatin C, β-trace protein, and β2-microglubulin) as an alternative to the creatinine-based CKD-EPI equation (CKD-EPIcr). This equation—the most used GFR-estimating equation—has recently been criticized for applying a discriminative term based on self-reported race.2 Inker et al convincingly demonstrated that their triple marker–based equation performs better than the CKD-EPI equation based on cystatin C only, a race-independent estimator.     
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        • PDF
      • Multiple-Biomarker Panel Estimated GFR Is Not Optimal or Cost-Effective
        American Journal of Kidney DiseasesVol. 77Issue 5
        • Preview
          The race-independent glomerular filtration rate (GFR) estimating equation with creatinine, cystatin C, β-trace protein (BTP), and β2-microglubulin (B2M) proposed by Inker et al1 as a replacement for creatinine-based equations is neither optimal nor cost-effective. In a recent study of 2,893 plasma proteins, 680 correlated with measured GFR (mGFR), with cystatin C showing the highest correlation, while B2M was not among the 8 best.2 The results by Inker et al show that the improvement of 1 – P30, when using the recommended cystatin C-B2M-BTP equation (1 – P30 = 15.6), rather than the one based only upon cystatin C (1 – P30 = 17.4), is not clinically significant and the lack of international calibrators for B2M and BTP will make it very difficult to reproduce this possible advantage in clinical practice.     
        • Full-Text
        • PDF