- Inker, Lesley A;
- Couture, Sara J;
- Tighiouart, Hocine;
- Abraham, Alison G;
- Beck, Gerald J;
- Feldman, Harold I;
- Greene, Tom;
- Gudnason, Vilmundur;
- Karger, Amy B;
- Eckfeldt, John H;
- Kasiske, Bertram L;
- Mauer, Michael;
- Navis, Gerjan;
- Poggio, Emilio D;
- Rossing, Peter;
- Shlipak, Michael G;
- Levey, Andrew S;
- Collaborators, CKD-EPI GFR;
- Andresdottir, Margret B;
- Gudmundsdottir, Hrefna;
- Indridason, Olafur S;
- Palsson, Runolfur;
- Kimmel, Paul;
- Weir, Matt;
- Kalil, Roberto;
- Pesavento, Todd;
- Porter, Anna;
- Taliercio, Jonathan;
- Hsu, Chi-yuan;
- Chen, Jing;
- Sinkeler, Steef;
- Wyatt, Christina;
- Krishnasami, Zipporah;
- Hellinger, James;
- Margolick, Joseph;
- Kingsley, Lawrence;
- Witt, Mallory;
- Wolinsky, Steven;
- Shafi, Tariq;
- Post, Wendy;
- Doria, Alessandro;
- Parving, Hans-Henrik
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.