Systematic review of international studies evaluating MDRD and CKD-EPI estimated glomerular filtration rate (eGFR) equations in Black adults

PLOS ONE, Oct 2022

Use of race adjustment in estimating glomerular filtration rate (eGFR) has been challenged given concerns that it may negatively impact the clinical care of Black patients, as it results in Black patients being systematically assigned higher eGFR values than non-Black patients. We conducted a systematic review to assess how well eGFR, with and without race adjustment, estimates measured GFR (mGFR) in Black adults globally. A search across multiple databases for articles published from 1999 to May 2021 that compared eGFR to mGFR and reported outcomes by Black race was performed. We included studies that assessed eGFR using the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPICr) creatinine equations. Risk of study bias and applicability were assessed with the QUality Assessment of Diagnostic Accuracy Studies-2. Of 13,167 citations identified, 12 met the data synthesis criteria (unique patient cohorts in which eGFR was compared to mGFR with and without race adjustment). The studies included patients with and without kidney disease from Africa (n = 6), the United States (n = 3), Europe (n = 2), and Brazil (n = 1). Of 11 CKD-EPI equation studies, all assessed bias, 8 assessed accuracy, 6 assessed precision, and 5 assessed correlation/concordance. Of 7 MDRD equation studies, all assessed bias, 6 assessed accuracy, 5 assessed precision, and 3 assessed correlation/concordance. The majority of studies found that removal of race adjustment improved bias, accuracy, and precision of eGFR equations for Black adults. Risk of study bias was often unclear, but applicability concerns were low. Our systematic review supports the need for future studies to be conducted in diverse populations to assess the possibility of alternative approaches for estimating GFR. This study additionally provides systematic-level evidence for the American Society of Nephrology—National Kidney Foundation Task Force efforts to pursue other options for GFR estimation.

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Systematic review of international studies evaluating MDRD and CKD-EPI estimated glomerular filtration rate (eGFR) equations in Black adults

PLOS ONE RESEARCH ARTICLE Systematic review of international studies evaluating MDRD and CKD-EPI estimated glomerular filtration rate (eGFR) equations in Black adults a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 OPEN ACCESS Citation: Umeukeje EM, Koonce TY, Kusnoor SV, Ulasi II, Kostelanetz S, Williams AM, et al. (2022) Systematic review of international studies evaluating MDRD and CKD-EPI estimated glomerular filtration rate (eGFR) equations in Black adults. PLoS ONE 17(10): e0276252. https://doi. org/10.1371/journal.pone.0276252 Ebele M. Umeukeje ID1,2☯, Taneya Y. Koonce ID3☯*, Sheila V. Kusnoor3,4, Ifeoma I. Ulasi5, Sophia Kostelanetz6, Annette M. Williams3, Mallory N. Blasingame3, Marcia I. Epelbaum ID3, Dario A. Giuse ID4, Annie N. Apple7, Karampreet Kaur7, Tavia González Peña7, Danika Barry ID8, Leo G. Eisenstein9, Cameron T. Nutt10, Nunzia B. Giuse3,4,11 1 Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States of America, 2 Vanderbilt Center for Kidney Disease, Vanderbilt University Medical Center, Nashville, TN, United States of America, 3 Center for Knowledge Management, Vanderbilt University Medical Center, Nashville, TN, United States of America, 4 Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, United States of America, 5 Renal Unit, Department of Medicine, College of Medicine, University of Nigeria/University of Nigeria Teaching Hospital, Ituku-Ozalla, Nigeria, 6 Division of General Internal Medicine and Public Health, Vanderbilt University Medical Center, Nashville, TN, United States of America, 7 Vanderbilt University School of Medicine, Nashville, TN, United States of America, 8 Department of Obstetrics & Gynecology, McGaw Medical Center of Northwestern University, Chicago, IL, United States of America, 9 Department of Medicine, NYU Langone Medical Center, New York, NY, United States of America, 10 Department of Medicine, Brigham and Women’s Hospital, Boston, MA, United States of America, 11 Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States of America ☯ These authors contributed equally to this work. * Editor: Karin Jandeleit-Dahm, Baker IDI Heart and Diabetes Institute, AUSTRALIA Abstract Received: January 6, 2022 Use of race adjustment in estimating glomerular filtration rate (eGFR) has been challenged given concerns that it may negatively impact the clinical care of Black patients, as it results in Black patients being systematically assigned higher eGFR values than non-Black patients. We conducted a systematic review to assess how well eGFR, with and without race adjustment, estimates measured GFR (mGFR) in Black adults globally. A search across multiple databases for articles published from 1999 to May 2021 that compared eGFR to mGFR and reported outcomes by Black race was performed. We included studies that assessed eGFR using the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPICr) creatinine equations. Risk of study bias and applicability were assessed with the QUality Assessment of Diagnostic Accuracy Studies-2. Of 13,167 citations identified, 12 met the data synthesis criteria (unique patient cohorts in which eGFR was compared to mGFR with and without race adjustment). The studies included patients with and without kidney disease from Africa (n = 6), the United States (n = 3), Europe (n = 2), and Brazil (n = 1). Of 11 CKD-EPI equation studies, all assessed bias, 8 assessed accuracy, 6 assessed precision, and 5 assessed correlation/ concordance. Of 7 MDRD equation studies, all assessed bias, 6 assessed accuracy, 5 assessed precision, and 3 assessed correlation/concordance. The majority of studies found Accepted: October 3, 2022 Published: October 18, 2022 Copyright: © 2022 Umeukeje et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the manuscript and its Supporting Information files. Funding: This study used the REDCap® database for data entry and collection; REDCap was provided by a Clinical and Translational Science Award UL1TR000445 from the National Center for Advancing Translational Sciences, https://ncats. nih.gov/. This work was supported in part by the National Institute of Diabetes and Digestive and PLOS ONE | https://doi.org/10.1371/journal.pone.0276252 October 18, 2022 1 / 17 PLOS ONE Kidney Diseases grant 1K23DK114566-01A1 (Umeukeje), the National Institute of Diabetes and Digestive and Kidney Diseases grant 1 R03 DK129626-01 (Umeukeje), https://www.niddk.nih. gov/, and the Agency for Healthcare Research and Quality grant T32HS026122 (Kostelanetz), https:// www.ahrq.gov/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Systematic review: Race adjustment in eGFR equations that removal of race adjustment improved bias, accuracy, and precision of eGFR equations for Black adults. Risk of study bias was often unclear, but applicability concerns were low. Our systematic review supports the need for future studies to be conducted in diverse populations to assess the possibility of alternative approaches for estimating GFR. This study additionally provides systematic-level evidence for the American Society of Nephrology— National Kidney Foundation Task Force efforts to pursue other options for GFR estimation. Competing interests: The authors have declared that no competing interests exist. Introduction Accurate assessment of kidney function is essential for proper diagnosis, staging, and management of chronic kidney disease (CKD). The gold standard for evaluating kidney function is measured glomerular filtration rate (mGFR), which relies on infusing chemicals, such as iothalamate, into the blood and quantifying urine clearance. Estimated GFR (eGFR) is based on the measurement of serum filtration markers, such as creatinine or cystatin C, and therefore is more practical to obtain in clinical practice [1]. The Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations are commonly used in the United States (U.S.) and internationally. Each includes serum creatinine measurement as a key variable for determining eGFR [2–4]. The equations were developed in large U.S. cohorts and include race, sex, and age variables [5]. Use of the race variable increases reported eGFR by 21.2% (MDRD) or 15.9% (CKD-EPI) in Black patients [3, 6]. While sex and age are biological variables, the meaning and classification of race have evolved over time. Definitions of race are often inconsistently applied, and the utility of race adjust (...truncated)


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Ebele M. Umeukeje, Taneya Y. Koonce, Sheila V. Kusnoor, Ifeoma I. Ulasi, Sophia Kostelanetz, Annette M. Williams, Mallory N. Blasingame, Marcia I. Epelbaum, Dario A. Giuse, Annie N. Apple, Karampreet Kaur, Tavia González Peña, Danika Barry, Leo G. Eisenstein, Cameron T. Nutt, Nunzia B. Giuse. Systematic review of international studies evaluating MDRD and CKD-EPI estimated glomerular filtration rate (eGFR) equations in Black adults, PLOS ONE, 2022, Volume 17, Issue 10, DOI: 10.1371/journal.pone.0276252