Lesley A Inker1, Sara J Couture2, Hocine Tighiouart3, Alison G Abraham4, Gerald J Beck5, Harold I Feldman6, Tom Greene7, Vilmundur Gudnason8, Amy B Karger9, John H Eckfeldt9, Bertram L Kasiske10, Michael Mauer11, Gerjan Navis12, Emilio D Poggio13, Peter Rossing14, Michael G Shlipak15, Andrew S Levey2. 1. Division of Nephrology, Tufts Medical Center; Tufts Clinical and Translational Science Institute, Tufts University, Boston, MA. Electronic address: linker@tuftsmedicalcenter.org. 2. Division of Nephrology, Tufts Medical Center; Tufts Clinical and Translational Science Institute, Tufts University, Boston, MA. 3. Institute for Clinical Research and Health Policy Studies, Tufts Medical Center; Tufts Clinical and Translational Science Institute, Tufts University, Boston, MA; Tufts Medical Center; Tufts Clinical and Translational Science Institute, Tufts University, Boston, MA. 4. Department of Epidemiology, John Hopkins Bloomberg School of Public Health, Baltimore, MD. 5. Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH. 6. Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, PA. 7. Department of Internal Medicine, University of Utah Health, Salt Lake City, UT. 8. Faculty of Medicine, University of Iceland, Reykjavik, Iceland; Icelandic Heart Association, Kopavogur, Iceland. 9. Departments of Laboratory Medicine and Pathology, University of Minnesota; Department of Medicine, Hennepin County Medical Center, Minneapolis, MN. 10. University of Minnesota; Department of Medicine, Hennepin County Medical Center, Minneapolis, MN. 11. Medicine, University of Minnesota; Department of Medicine, Hennepin County Medical Center, Minneapolis, MN. 12. Faculty of Medical Sciences, University Medical Center Groningen, Groningen, The Netherlands. 13. Department of Nephrology and Hypertension, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH. 14. Steno Diabetes Center Copenhagen and Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. 15. Kidney Health Research Collaborative, San Francisco Veterans Affairs Medical Center, University of California, San Francisco, CA.
Abstract
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.
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.
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