SPECIAL ARTICLE www.jasn.org

Reassessing the Inclusion of Race in Diagnosing Kidney Diseases: An Interim Report from the NKF-ASN Task Force

Cynthia Delgado,1 Mukta Baweja,2 Nilka Ríos Burrows,3 Deidra C. Crews ,4 Nwamaka D. Eneanya ,5 Crystal A. Gadegbeku,6 Lesley A. Inker,7 Mallika L. Mendu,8 W. Greg Miller,9 Marva M. Moxey-Mims,10 Glenda V. Roberts,11 Wendy L. St. Peter ,12 Curtis Warfield,13 and Neil R. Powe14

Due to the number of contributing authors, the affiliations are listed at the end of this article.

ABSTRACT For almost two decades, equations that use serum creatinine, age, sex, and race to On a national scale, eGFR is used for eGFR have included “race” as Black or non-Black. Given considerable evidence of important surveillance and regulatory disparities in health and healthcare delivery in African American communities, some purposes, including population tracking regard keeping a race term in GFR equations as a practice that differentially influ- of kidney diseases by the Centers for Dis- ences access to care and kidney transplantation. Others assert that race captures ease Control and Prevention and the important GFR determinants and its removal from the calculation may perpetuate United States Renal Data System, re- other disparities. The National Kidney Foundation (NKF) and American Society of search supported by the National Insti- Nephrology (ASN) established a task force in 2020 to reassess the inclusion of race in tutes of Health (NIH) and other public the estimation of GFR in the United States and its implications for diagnosis and and private funding agencies (including subsequent management of patients with, or at risk for, kidney diseases. This interim ongoing clinical trials), and eligibility for report details the process, initial assessment of evidence, and values defined re- kidney-disease education or nutritional garding the use of race to estimate GFR. We organized activities in phases: (1) clarify supplementation under the Medicare the problem and examine evidence, (2) evaluate different approaches to address program.2–5 Although GFR estimation use of race in GFR estimation, and (3) make recommendations. In phase one, we has remained an important guide for constructed statements about the evidence and defined values regarding equity clinical decision making and population and disparities; race and racism; GFR measurement, estimation, and equation per- tracking, derived equations, like many formance; laboratory standardization; and patient perspectives. We also identified other tools in medicine, have undergone several approaches to estimate GFR and a set of attributes to evaluate these ap- proaches. Building on evidence and values, the attributes of alternative approaches to estimate GFR will be evaluated in the next phases and recommendations will C.D. and N.R.P. are co-chairs of the NKF-ASN Task be made. Force. This article is being published concurrently in the JASN 32: ccc–ccc, 2021. doi: https://doi.org/10.1681/ASN.2021010039 Journal of the American Society of Nephrology and American Journal of Kidney Diseases. The articles are identical except for stylistic changes in keeping with each journal’s style. Either of these versions The measurement of creatinine, the tomography scans or cardiac catheteriza- may be used in citing this article. muscle protein metabolite, in serum is tions. Almost all clinical laboratories in the Published online ahead of print. Publication date used to estimate kidney function as United States now report eGFR with any available at www.jasn.org. eGFR and has served as a major marker laboratory metabolic panel that contains Correspondence: Dr. Cynthia Delgado, San Fran- for the detection, diagnosis, and manage- serum creatinine, with one estimate for Af- cisco VA Medical Center, Nephrology Section, 111J4150 Clement Street, San Francisco, CA ment of kidney diseases. Creatinine-based rican Americans and another for non- 94121, or Dr. Neil R. Powe, Department of Medi- eGFR (eGFRcr) thresholds guide clinical African Americans.1 Useofraceinmedical cine, Priscilla Chan and Mark Zuckerberg San practice, including estimation of surgical practice has come under scrutiny in light of Francisco General Hospital and University of Cal- ifornia San Francisco, San Francisco, CA 94110. Email: complication risk; initiation, discontin- the most recent reckoning with racism and [email protected] or [email protected] uation, and dosing of medications; and publicly displayed atrocities against racial Copyright © 2021 by the American Society of utilization of certain contrast-based and ethnic minorities across the United Nephrology and the National Kidney Foundation, tests and procedures, such as computed States that has been longstanding. Inc. All rights reserved.

JASN 32: ccc–ccc, 2021 ISSN : 1046-6673/3205-ccc 1 SPECIAL ARTICLE www.jasn.org a nearly 50-year history of re-evaluation, measured GFR as their White adult Estimated GFR from cystatin C is not adaptation, and refinement. This evolu- counterparts, indicating that determi- more accurate than eGFRcr; however, tion continues in the reassessment of the nants of serum creatinine levels, other the equation reported in 2012, with a use of race in estimating GFR. than GFR, differed between the groups.8 combination of the two markers, pro- Race was among the 16 factors con- vides more accurate estimates.12 A term sidered in the derivations and refine- for African American race is included in EVOLUTION OF KIDNEY ment of the Modification of Diet in this combined marker equation that is FUNCTION–ESTIMATING Renal Disease (MDRD) Study equation substantially smaller than in the EQUATIONS reported in 1999.8 In regression models creatinine-only equations (1.08). In the to predict GFR from serum creatinine report of the equation, the investigators Since 1976, equations developed to esti- levels, a term (and coefficient) for self- noted an insufficient number of African mate the clearance or filtration function identified African American race was Americans were included in the valida- of the kidney from serum creatinine found to be a substantial and statistically tion datasets, prohibiting validation of concentration have included, and ad- significant predictor of carefully mea- the effect of this coefficient in a separate justed for, various factors, including sured GFR.8 The MDRD equation was population outside of the development age, sex, African American race, and/or validated in the African American Study population. body weight. These equations were of Kidney Disease.9 At the time, this ad- Clinical practice guidelines from Kid- largely developed using clinical, epidemi- justment was thought to be an advance ney Disease Improving Global Out- ologic, and statistical methods that were, because an important group, with high comes (KDIGO) recommend that, at the time of equation derivation, con- risk for CKD progression, was included whenever serum creatinine is measured sidered to be scientifically state of the art. in studies of measured GFR. in clinical practice, an eGFR should be The Cockcroft–Gault equation, one In 2009, the Chronic Kidney Disease reported with an eGFRcr, using the of the initial equations, used data from Epidemiology Collaboration (CKD- CKD-EPI 2009 creatinine equation or a 249 White males with measured creati- EPI) equation using creatinine was de- similarly accurate equation. When a nine clearance ranging from 30 to veloped in a subsequent analysis with more accurate assessment of GFR is re- 130 ml/m2 to estimate creatinine clear- pooled studies of individual partici- quired, or there are concerns about the ance.6 Although this equation represents pants. Meta-analytic regression was accuracy of eGFRcr, this initial test one of the initial attempts to approxi- used in a more heterogeneous partici- should be followed by a confirmatory mate kidney function without needing pant population, which combined data test using eGFR computed by cystatin to undergo laborious and potentially in- from thousands of individuals (includ- C (alone or in combination with creati- complete urine collection, the derivation ing White, African American, and—to a nine), measured creatinine clearance, or cohort was limited by lack of both race far lesser extent—Asian, Hispanic/La- measured GFR.13 Since the first eGFR and sex diversity. tino, and Native American individuals) equations were introduced two decades from ten different independent studies. ago, data from laboratories in the United Results were validated in a pooled group States show continual growth in the re- RACE IN EGFR ASSESSMENT IN of 16 separate studies.10 Across these porting of eGFR along with serum cre- THE UNITED STATES studies, investigators found a similar atinine and, despite KDIGO guidelines, result for African American race as a pre- the MDRD equation is the most fre- After the publication and use of the dictor of measured GFR, with the mag- quently used.14 Cockcroft–Gaultequationandbefore nitude of the coefficient slightly less than the derivation of subsequent equations, that in the MDRD Study equation (1.20 published research by the National Insti- compared with White individuals for the PROBING THE RATIONALE FOR A tute of Diabetes and Digestive and MDRD Study equation, and 1.16 com- RACE COEFFICIENT Kidney Diseases (NIDDK) showed that pared with non-Black individuals for the serum creatinine concentrations were CKD-EPI equation). In studies of mea- Although the biologic rationale for in- higher among non-Hispanic Black sured GFR in the United States, other cluding coefficients (such as age, sex, adults when compared with non- racial and ethnic groups were not and body weight) in eGFR equations Hispanic White adults.7 This research included in large enough numbers to seem apparent, the reasons for including was based on the Third National Health understand whether differences in non- race on the basis of serum creatinine ob- and Nutrition Examination Survey, a na- GFR determinants of creatinine are servational data, muscle mass, and/or tionally representative sample of the US present in persons of non-White and other factors are questionable.15 It may population. Subsequent research by non-Black race or ethnicity.11 be problematic to rely on a correction Levey and others found that serum cre- An alternative filtration marker, cys- without completely understanding atinine levels were higher among African tatin C, is available and does not include what factors are being captured together, American adults who had the same race in its estimating equation for GFR. and with an underappreciation of the

2 JASN JASN 32: ccc–ccc,2021 www.jasn.org SPECIAL ARTICLE ancestral diversity among African Amer- DISPARITIES IN HEALTH AND related to kidney disease. Multifaceted icans which exists in other racial and HEALTHCARE initiatives beyond an examination of ethnic groups.16 There is well-known GFR-estimating equations are impor- exploitation and inhumane experi- Studies have shown disparities in tant to address, and ultimately eliminate, mentation to which racial and ethnic health and healthcare disproportion- disparities. minority individuals, particularly Afri- ately affect African Americans. When can Americans, have been subjected.17 compared with non-Hispanic White As a small, but growing, number of US individuals, African Americans have FORMATION OF THE NKF-ASN individuals self-identify as being of nearly double the prevalence of hyper- TASK FORCE mixed racial background, the complex- tension, a common etiology of kidney ity of a changing racial and ethnic com- disease.30–32 Decline in GFR among The National Kidney Foundation (NKF) position makes the use of race in the African Americans occurs at an earlier and the American Society of Nephrology practice of medicine further problem- age and at a faster annualized rate when (ASN) announced on July 2, 2020 plans atic. Recent calls for social justice re- compared with non-Hispanic White to establish a task force to reassess the Americans, even by cystatin C–based form have galvanized segments of the inclusion of race in diagnosing kidney medical community into further dis- GFR assessment.33 African Americans disease. Representing patients, health- course and action toward achieving with advanced kidney disease are youn- care professionals, and other advocates greater healthcare equity, including ger, with an incidence of ESKD nearly across the world,42 NKF and ASN are the assertion of race as a social, non- three times that of their non-Hispanic two leading organizations dedicated to biologic, construct.18–24 White counterparts.5 preventing, treating, and ultimately cur- Many assert that removing race from Such disparities go beyond the bur- ing kidney disease. During the past two estimating GFR would achieve better den of kidney diseases and extend into decades, both organizations have differences in kidney-disease treatment. health and healthcare equity by miti- championed health equity and health- gating disparities, particularly for Before the widespread use of GFR esti- care disparities in kidney disease. The African American patients who experi- mation, it was documented that African formation of the joint task force is a ence faster progression to kidney fail- Americans were more likely to receive a strong affirmation of both organiza- ure and lower rates of transplantation. late referral for an evaluation by a ne- tions’ commitment to health equity, di- This rationale posits that such a change phrologist, a finding that is associated versity, and scientific evidence. wouldresultinearlieridentifica- with decreased survival after the devel- A decision to remove race from the tion and management of kidney dis- opment of ESKD.34 Documented since estimation of GFR is not trivial and the 1980s and 1990s, African Americans eases for African American patients, could have consequences. As such, referral for specialist care by nephrolo- are less likely to be treated with home NKF and ASN charged the task force gists, and earlier referral for kidney dialysis therapies and to be waitlisted with: transplantation.25–27 Others assert for kidney transplant, with even fewer 5,35–38 that, even if previously observed racial being transplanted. The reasons c Examining the inclusion of race in the differences are poorly understood, race for observed disparities are multifac- estimation of GFR and its implica- is capturing important determinants of torial and may be attributed to inter- tions for the diagnosis and subsequent measured GFR. This rationale posits nalized, personal, or institutionalized management of patients with, or at 39,40 that removing race may create or per- racism. To date, disparities in health risk for, kidney disease. petuate other disparities by assigning and healthcare have not been conclu- the value for non-African Americans sively attributed to race correction in c Recognizing that any change in eGFR to African Americans.17,28,29 There is eGFR equations, although research is reporting must consider the multiple also a concern of subjectivity in regards ongoing. social and clinical implications, be to applying the African American race Whereas Medicare spends approxi- based on rigorous science, and be coefficientonhealthcaredecisionmak- mately $120 billion annually on people part of a national conversation about ing, and personal and/or provider bias with kidney diseases (including .$70 uniform reporting of eGFR across in transparency with patient-physician billion for people with non–dialysis- healthcare systems. communication. These points of view, dependent kidney disease), the NIH along with others, have highlighted the budget on kidney research is ,$700 mil- c Incorporating the concerns of pa- need to find an approach to GFR esti- lion, and little has been allocated to the tients and the public, especially in mation that embraces the substantial understanding of racial disparities in marginalized and disadvantaged diversity of the US population and pro- kidney-disease care and outcomes.5,41 communities, while rigorously as- motes social and health equity without Reassessing race in eGFR should be the sessing the underlying scientificand creating new, or worsening current, start of reassessing race in other areas of ethical issues embedded in current health disparities. diagnosis and management decisions practice.

JASN 32: ccc–ccc, 2021 Reassessing Race in eGFR 3 SPECIAL ARTICLE www.jasn.org c Ensuring that GFR estimation equa- deliberations, including: (1) embracing forward to final recommendations. Task tions provide an unbiased assessment a holistic approach that examines the force moderators devised goals for each of GFR so that laboratories, clinicians, clinical, psychosocial, and financial session, an agenda, and an outline of patients, and public-health officials tradeoffs of benefits and harms, balanc- specificquestionsforwhichthetask can make informed decisions to en- ing them across racial/ethnic groups force sought information. For example, sure equity and personalized care for with particular attention to how kidney a session on race and racism included an patients with kidney disease. diseases affect different races; (2)being in-depth review of the definitions of race data driven and generating a solution and racism, and the effect of internal- c Keeping laboratories, clinicians, and driven by science and evidence; and (3) ized, personal, and institutional racism other kidney health professionals ap- engaging in effective listening, respect- on health and healthcare disparities. The prised of any potential long-term ing different ideas and opinions, and task force defined and discussed genetic implications of removing race from having a willingness to learn after hear- ancestry and its relation with self- the eGFR formula. ing all perspectives. reported race; examined studies on the Importantly, the NKF-ASN leader- relation of genetic ancestry to serum cre- The task force was created to include ship and the members of the task force atinine levels; and evaluated the history a variety of health professionals and pa- collectively agreed on the confidentiality of GFR measurement and the underly- tients, including individuals with exper- of deliberations (including refraining ing physiology, study design, popula- tise in diagnosis, management, and from social media commentary) to pro- tions, and statistical methods used for treatment of kidney disease; measure- mote candid opinions and exchange of the derivation of the most commonly ment and estimation of GFR; healthcare ideas. Members also mutually agreed to used GFR-estimating equations. disparities; epidemiology and clinical re- work toward the goal of agreement in Equation examination included an search; laboratory medicine; pharmacy; instances where there were differences intensive review of the race, ethnicity, health services research; patient safety; of opinion. All task force weekly sessions and socioeconomic and clinical charac- patient experience with care; patient were held virtually due to social distanc- teristics of participants in the studies in- quality of life; medical education; and ing directives during the coronavirus corporating the gold standard of direct prevention/public health. The NKF and disease 2019 pandemic. measurement of GFR included in equa- ASN leadership selected the cochairs and To undertake a comprehensive and tion derivation. Substantial heterogene- initial members, recognizing the need in-depth exploration of several issues ity exists across individual studies and, for varying perspectives and back- germanetoraceandGFRestimation, therefore, the task force evaluated ap- grounds, requisite expertise, interest, the task force organized its activities proaches for pooling data from different and ability to commit to the intensive into three phases (Table 1). This interim cohorts (i.e., meta-analysis) for a more deliberations that lie ahead. The cochairs report focuses on phase one. comprehensive and diverse sample of additionally suggested to NKF and ASN people for equation derivation. The that they appoint patients, an expert in Phase One task force also explored past efforts to drug dosing and US Food and Drug Ad- In phase one, the task force clarified achieve consistency in eGFR measure- ministration (FDA) considerations, and the problem and evidence by examining ment and reporting across US clinical an expert on public-health surveillance. information, including testimony, laboratories and institutions through Patients were explicitly included as lectures, and literature from experts standardization of laboratory measure- members because of the importance of (Table 2). First, the members of the ments and promulgation of clinical their voice and the effects any potential task force collectively identified and de- practice guidelines. Finally, the task force change could have on their health and cided upon the domains to be consid- considered patients’ perspectives and the well-being. Task force members are not ered and the panelists and discussants role of shared decision making in the de- remunerated. Disclosures are included to be formally invited by the cochairs livery of healthcare. After each session, at the end of the manuscript. and NKF-ASN leadership to provide ex- members of the task force debriefed pri- pert testimony. We sought a wide range vately to discuss and summarize invited of evidence and views, as illustrated by testimony and independent literature re- NKF-ASN TASK FORCE PROCESS representation across the United States. viewed. On the basis of this informa- We assured confidentiality to individuals tion, the task force developed a series During the initial meeting of the task who provided testimony, in some in- of statements that summarized the evi- force, members stated their familiarity stances due to sharing of unpublished dence and values held by its members and involvement with the issues and bia- information. Members of the task force regarding health and healthcare equity, ses so that other members of the task with subject-matter expertise served as disparities, race and racism, GFR, stan- force were aware of individual initial subject moderators so that no one task dardization, and patients’ perspectives leanings. The task force then established force member unduly influenced the en- (Table 3). All members of the task force principles to guide its interactions and tire process, an approach to be followed actively participated in constructing the

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Table 1. Overview of work phases and activities of the NKF-ASN Task Force Phase One Phase Two Phase Three Clarifying the problem and evidence Evaluating the approaches Making recommendations eGFR and measurement Clinical consequences of different approaches Issuance of recommendations Race, racism, and genetic ancestry. System and societal consequences of different approaches Comment on recommendations Body composition and populations Implementation used in eGFR estimation Standardization and guidelines Patients’ perspective and shared decision making Possible approaches to address race in GFR estimation (Table 4)

statements of evidence and value, scru- kidney diseases in African Americans approaches on patient safety and health tinizing and revising them. Revisions in- and all other races/ethnicities, how equity put forth in this report (https:// cluded a series of iterations regarding such changes might affect US FDA ap- form.jotform.com/210244230676145). content, language, and perspective. proval and labeling of therapies, and the All of this information will be used to The task force then assembled an in- possible effect on the federal govern- make future recommendations. clusive inventory of potential approaches ment’s tracking of kidney diseases In phase three, the task force will de- to GFR estimation or measurement require further examination. The avail- velop recommendations on the basis of that included approaches in which race ability in communities of assays for a number of attributes (Table 5). These is considered and not considered in newer, raceless biomarkers (e.g.,cystatin attributes include biomarker choice, in- derivation and/or reporting of eGFR C, b-trace protein, b2 microglobulin) puts and their availability for estimation (Table 4). The approaches included also need evaluation.76,96 and reporting, representation of diver- those (1) currently in widespread use sity in participants in research founda- (including race in eGFR equations), (2) Phases Two and Three tional to equation development, and recently adopted at some institutions, Recognizing the use of race in estimat- equation bias and accuracy compared (3) currently available that might be am- ing equations is problematic, the task with measured GFR for different race plified more broadly, and (4)recently force has focused on identifying a path and ethnic groups. Importantly, attri- suggested that are currently under devel- forward. In phase two, on the basis of butes also include consequences for opment or could be developed. testimony, lectures from additional ex- clinical decisions with regard to evalua- Final recommendations will be made perts, literature, and input from the tion and management of patients’ GFR after the task force examines the community of interested individuals and feasibility of standardization. Fi- strengths and weaknesses of existing and organizations, the task force will nally, it is very important that any rec- and newer approaches to estimating evaluate each of the possible ap- ommended approach incorporates the GFR. The downstream consequences of proaches that could be recommended patient perspective and be patient changes from current reporting are un- with regard to its patient, clinical, centered.97 known and could be profound. Changes health system, and societal effects Recommendations will be reviewed could lead to overdiagnosis or under- (Supplemental Materials 1 and 2). and informed by an advisory board, in- diagnosis of kidney diseases as a result The deliberations and conclusions of cluding members of the NKF’sand of GFR estimation bias and inaccuracy these meetings will be presented in de- ASN’s governing bodies, committees on for any ethnic group. Conclusive evidence tail in the final report. diversity and inclusion, policy and advo- on outcomes from well-conducted studies The task force held a series of forums cacy panels, and experts in patient safety will likely take years to produce. The re- in January 2021 to invite input from and healthcare quality. The task force is sultant effects in terms of the numbers of the broader kidney community (Public committed to continuing its transpar- African Americans affected and the Forums to Provide Input to eGFR ent, open, and community-based pro- safety and effectiveness of pharmacother- Joint Task Force, NKF). Over the course cess through phases two and three. apy use and dosing need appraisal. Addi- of three sessions, the task force heard tionally, effect on managing risk factors from (1) students and trainees; (2) (e.g., hypertension), nephrology referral, clinicians, scientists, and other health SUMMARY AND IMPLICATIONS transplant waitlisting, and kidney dona- professionals; and (3)patients,family tion will also warrant evaluation. members, and other public stake- Estimation of GFR is a major underpin- The ramifications of changes in eGFR holders. The task force also seeks input ning of many clinical decisions in med- equations on research studies examining regarding the effect of particular icine. The use of race to estimate GFR

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Table 2. Topics and panelists/discussants during phase one Topic Moderators and Panelists/Discussants Location GFR: history and evolution of kidney Neil Powe, MD, MPH, MBA; Cynthia Delgado, MD function measurement over the past Andrew S. Levey, MD Boston, Massachusetts 50 years GFR: measurement, estimation, Lesley Inker, MD performance in the United States Josef Coresh, MD, MPH Baltimore, Maryland Susan L. Furth, MD, PhD Philadelphia, Pennsylvania Andrew S. Levey, MD Boston, Massachusetts Julia B. Lewis, MD Nashville, Tennessee Robert G. Nelson, MD, PhD Bethesda, Maryland Derek K. Ng, PhD Baltimore, Maryland Andrew D. Rule, MD Rochester, Minnesota George Schwartz, MD Rochester, New York Race and racism; genetic ancestry and Deidra Crews, MD, ScM race; creatinine, race and ancestry Camara Phyllis Jones, MD, PhDa Atlanta, Georgia David R. Williams, PhDa Boston, Massachusetts Dorothy E. Roberts, JDa Philadelphia, Pennsylvania Nora Franceschini, MD Chapel Hill, North Carolina Alicia R. Martin, PhD Boston, Massachusetts Miriam S. Udler, MD, PhD Baston, Massachusetts Esteban G. Burchard, MD San Francisco, California Jeffery B. Kopp, MD Bethesda, Maryland Opeyemi A. Olabisi, MD, PhD Durham, North Carolina Body composition and populations used Cynthia Delgado, MD in eGFR estimation Kamyar Kalantar Zadeh, MD, PhD Los Angeles, California Andrew D. Rule, MD Rochester, Minnesota Glen M. Chertow, MD Palo Alto, California Kirsten L. Johansen, MD Minneapolis, Minnesota Baback Roshanravan, MD Davis, California Flor Alvorado, MD Baltimore Maryland Abinet M. Aklilu, MD New Haven, Connecticut Laboratory standardization issues with Greg Miller, PhD; Mukta Baweja, MD markers and guidelines Adeera Levin, MD, FRCPC Vancouver, British Columbia Amy D. Karger, MD, PhD Minneapolis, Minnesota Andrew S. Narva, MD Washington, DC Harvey Kaufman, MD, FCAP, MBA Short Hills, New Jersey Holly J. Kramer, MD, MPH Maywood, Illinois James Fleming, PhD, FACB Greensboro, North Carolina Joseph A. Vassalotti, MD New York, New York Neil Greenberg, PhD, DABCC Cleveland, Ohio Ravi I. Thadhani, MD, MPH Boston, Massachusetts Wolfgang C. Winkelmayer, MD, ScD Houston, Texas W. Greg Miller, PhD Richmond, Virginia Patient perspective and participatory Glenda Roberts, BSc; Curtis Warfield, MS decision-making experience and Monica Peek, MD, MPH Chicago, Illinois patient centered considerations David White Brooklyn, New York Richard Knight Bowie, Maryland Keren Ladin Medford, Massachusetts Kevin Fowler Chicago, Illinois Rajnish Mehrotra, MD Seattle, Washington Allison Tong, PhD, MPHb Sydney, Australia L. Ebony Boulware, MD Durham, North Carolina H. Gilbert Welch, MD Boston, Massachusetts Possible approaches to address race in Neil Powe, MD, MPH, MBA; Cynthia Delgado, MD GFR estimation Task Force Members aPreviously disseminated video talks were reviewed for these individuals due to their availability. bVideo talk was reviewed for this individual due to their availability.

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Table 3. NKF-ASN Task Force agreed upon statements of evidence and value Statement: Evidence or Value Equity and disparities (1) Equitya in kidney health and kidney healthcare is a fundamental and important goal. (V) (2) Disparities in kidney health and kidney health care should not exist. (V) (3) Equity in healthcare, as defined by the NAM is care that does not vary in quality on the basis of personal characteristics, such as sex, race/ ethnicity, geographic location, or socioeconomic status.43 (E) (4) A disparity in healthcare, as defined by NAM, is a difference in care that arises through operation of the healthcare system; legal or regulatory climate; or discrimination, biases, stereotyping, and uncertainty; but is not due to clinical appropriateness or patient preference.44 (E) (5) A variety of factors influence kidney health across racial and ethnic groups, including delivery of healthcare, clinical/health policies, environment, genetics, and health behaviors.45–51 (E) These factors act with a different degree of influence along the life span of individuals and along the continuum from health to kidney disease.45–49 (E) There are gaps in our understanding of these influences and how to interrupt their effect on creating health disparities.52 (E) To eliminate disparities, multifaceted initiatives beyond an examination of estimating equations must be developed. (V) (6) Differences in health exist across racial and ethnic groups in the United States, and not all of these differences are accounted for by socioeconomic status, geographic regions (including urban versus rural setting), insurance, lifestyle, and clinical factors.53 (E) Disparities in healthcare exist across racial and ethnic groups and geographic regions (including urban versus rural setting) in the United States, even after accounting for insurance status, income, age, and disease severity.44,54 (E) (7) Disparities across racial and ethnic groups in the United States exist in kidney disease. These disparities exist with regard to kidney-disease risk factors, comorbidities, and progression to kidney failure.2,5,55 (E) Disparities across racial and ethnic groups in the United States exist in kidney- disease care, including diabetes and BP control, nephrology referral, dialysis modality, and transplantation, and with regard to both living and deceased kidney donation.56–58 (E) Disparities across racial and ethnic groups in the United States in healthcare exist for diagnostics and therapeutics, which rely on GFR assessment (e.g., radiocontrast administration; metformin, anticoagulant, and chemotherapeutic use).59–62 (E) (8) Racial and ethnic diversity in participants in health and healthcare research is an important component of equity for studies and their data to be useful and generalizable to decisions in routine clinical practice.17,63,64 (E) Research studies should focus on a diversity of racial and ethnic groups to allow for greater generalizability. (V) Race and racism (9)Raceisdefined as a construct of human variability based on perceived differences in biology, physical appearance, and behavior.65 (E) Race and ethnicity are social and not biologic constructs.17,66,67 (E) (10) Racism is defined as an organized system, rooted in an ideology of inferiority that categorizes, ranks, and differentially allocates societal resources to human population groups.68 (E) Racism can be internalized, personal, or institutional.40 (E) As such, racism can be a part of the environment/behavior, delivery of healthcare, and clinical/health policy factors, respectively.69 (E) Racism can impede prevention and clinical care along the continuum from healthy kidneys, to kidney disease, to treatment.39,70 (E) Implicit bias has also been shown to negatively affect patient outcomes, particularly among African American patients in the United States.71 (E) Approaches proven to minimize implicit bias in healthcare delivery should be used. (V) The effects of racism can be long lasting and this effect may even be carried forward over generations.72–74 (E) (11) Although race and genetic ancestry are related, race captures factors beyond genetic ancestry. The relation between race, ancestry, and observed biology is poorly understood.17 (E) Research is ongoing to elucidate the relation between genetic ancestry and race.17 (E) (12) According to 2019 US Census population estimates, the self-identified racial and ethnic composition of individuals was 76.3% White, 13.4% African Americans, 5.9% Asian, 1.3% American Indian/Native American and Alaskan Native, 0.2% Native Hawaiian and Other Pacific Islander, with approximately 18.5% Hispanic/Latinx ethnicity.75 (E) Approximately 2.9% of US individuals self-identified as being of mixed racial background.75 (E) The complexity of changing racial and ethnic makeup makes the use of race in the practice of medicine challenging and potentially problematic. (V) GFR measurement, estimation, and equation performance (13) Creatinine and cystatin C are the most commonly used and studied filtration markers for use in estimating GFR.13 (E) Creatinine is used more commonly, is more widely available, and has a longer history of study than cystatin C.8,10,76 (E) The determinants of serum concentrations of creatinine are not completely understood, and those of cystatin C are even less well understood.77 (E) Assays for cystatin C have greater analytical variation than do assays for creatinine.78 (E) (14) Over 250 million serum creatinines are performed each year in the United States. The cost for serum creatinine is currently low relative to serum cystatin C (Medicare reimbursement rates in 2020, $5.12 and $18.52, respectively).79 (E) With more widespread adoption and use of cystatin C, costs could decrease. (V) (15) Multiple studies among the US population, including national health statistics studies across age groups, show African American men and African American women have higher serum creatinine concentrations than their White counterparts. Not all factors that might affect serum creatinine concentrations were accounted for in these studies.7,80 (E) Studies have also shown African Americans have higher serum creatinine concentrations than White individuals at the same measured GFR in the United States.81 (E) The reasons for these differences are not understood.81 (E) (16) Studies have shown the proportion of African ancestry is related to the level of creatinine in US adults.82,83 (E) Studies have not examined the relation of genetic ancestry to measured GFR. (E) These studies are desired. (V)

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Table 3. Continued

Statement: Evidence or Value (17) All estimates of GFR are subject to bias, imprecision, and inaccuracy.8,10,76,84 (E) Equations should not differentially induce bias and inaccuracy by age, sex, or race; i.e., they should not have disproportionate bias, imprecision, or inaccuracy for a particular group according to age, sex, or race. (V) (18) Clinical algorithms to assess eGFR with additional predictors are a better indicator of GFR than serum creatinine concentration alone.13 (E) (19) Individual studies of adults with measured GFR and eGFRcr or eGFRcys have been limited in the diversity of participants with regard to age, sex, race, ethnicity, geography, socioeconomic status, comorbidity, and other risk factors for kidney disease. These individual studies have also been limited in diversity of participants with regard to absence, severity, and etiology of kidney disease.8,10,76,81 (E) Individual studies of adults are also limited in measurements of body composition and chronic or acute illness.8,12,76 (E) Future studies should seek more diversity in participants with regard to many patient characteristics (age; sex; race; ethnicity; geography; socioeconomic status; comorbidity; risk factors for kidney disease; absence, severity, and etiology of kidney disease; diet; and body composition). (V) (20) Estimating equations that were not developed in diverse populations (including race and ethnicity) leads to questions as to how applicable they are to populations not included in the developmental phase without further validation. (V) (21) To estimate GFR, it is useful to pool data on participants from individual studies (i.e., meta-analysis) to obtain a more comprehensive and diverse sample of people (age; sex; race; ethnicity; geography; socioeconomic status; comorbidity; risk factors for kidney disease; absence, severity, and etiology of kidney disease; and body composition) for whom eGFR can be applied in clinical practice. (V) (22) To approximate measured GFR with greater accuracy and to minimize bias in all groups, creatinine-based estimating equations (MDRD and CKD-EPI eGFRcr or eGFRcr-cys) have included a coefficient for age, sex, and race; whereas cystatin C–based equations (CKD-EPI) have included coefficients for age and sex alone.12 (E) (23) Data in adult ambulatory outpatients show that the most validated equations (CKD-EPI; eGFRcr, eGFRcys, and eGFRcr-cys) perform with different degrees of bias and accuracy.12 (E) With regard to accuracy, CKD-EPI 2012 eGFRcr-cys has the highest available accuracy (P30, accuracy measured as the percentage of estimates within 30% of measured GFR) at 91.5%, with similar accuracy for CKD-EPI 2009 eGFRcr at 87.2% and CKD-EPI 2012 eGFRcys at 86.9%.12 (E) Precision (interquartile range) is best for eGFRcr-cys (13.4) and less for eGFRcr (15.4) and eGFRcys (16.4), all in ml/min per 1.73 m2.12 (E) Bias (measured minus estimated GFR) is similar among equations: eGFRcr-cys (3.9), GFRcr (3.7), and eGFRcys (3.4), all in ml/min per 1.73 m2.12 (E) Bias and inaccuracy of estimated GFR equations are greater at higher measured GFR.12 (E) There is no differential accuracy, precision, or bias in equations between Black and non-Black individuals using these equations.12 (E) (24) Inclusion of height and total body weight did not improve performance of eGFR estimation in adults.11,85 (E) Validated equations for use in children include height, serum creatinine, cystatin c, and BUN, but do not include race.86 (E) Although methods for measuring body composition have been useful in research settings, no single method has been widely standardized and adapted for routine clinical use for adults in the United States or evaluated for use with eGFR equations. (V) Laboratory standardization (25) Standardization of measurement and reporting of GFR in the United States is important. (V) (26) Standardization can be achieved through issuance and adherence to clinical practice guidelines.87 (E) (27) Reference materials, methods, and accounting for interfering substances are important in achieving assay equivalence.1,88,89 (E) Results for analytes used to estimate GFR should be standardized. (V) (28) Implementation efforts to achieve standardization, and adoption and adherence to practice guidelines, are important for uniform practices. (V) (29) Clinical laboratories and the manufacturers of laboratory equipment and supplies must be engaged to achieve standardization. (V) Patients’ perspective (30) Patients prefer to have shared decision making with their physician, rather than the patient or the physician being the sole decision maker.90 (E) Given the diversity of the patient populations within and across healthcare settings, patient education on the clinical implications of eGFR should include a discussion on how the equation was derived, its limitations, and how it applies to them. (V) The task force actively participated in constructing the statements of evidence and value, the statements then underwent scrutiny and revision by all of the members of the task force. The task force went through a series of iterations regarding content, language, and perspective. V, value; NAM, National Academy of Medicine; E, evidence; eGFRcys, estimated GFR from cystatin C; eGFRcr-cyst, estimated GFR from creatinine and cystatin C; P30, accuracy measured as the percentage of estimates within 30% of measured GFR. aSee Supplemental Material 2 for terms and definitions.

and possible replacements have short- Because these differing approaches public-health professionals—the task comings that the task force is currently may have varying effects for patients force would like to offer a careful and examining. Nationwide, many institu- treated and followed by clinicians— judicious review to guide implementa- tions have made independent decisions including but not limited to primary tion efforts for a standardized and equi- to address race in estimation of GFR, but care physicians, medical specialists table approach to care. The task force these approaches vary and, therefore, GFR (e.g., nephrologists, hospitalists, endo- understands how high the stakes are for estimates and subsequent care decisions crinologists, cardiologists, oncologists), African Americans, recognizes that ex- are not standardized. surgical specialists, pharmacists, and peditious recommendations are needed,

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Table 4. Inventory of possible approaches to estimating and reporting GFR for general use Creatinine Used as Biomarker Noncreatinine Biomarker Used Estimation and reporting with creatinine and race using existing Estimation with cystatin C, creatinine, and race using existing equations equations (1) eGFRcr (MDRD or CKD-EPI) (age, sex, race) with “Black” estimate (13) eGFRcr-cys (CKD-EPI) (age, sex, race) with “Black” estimate reported for self-identified African Americans and “non-Black” reported for self-identified African Americans and “non-Black” estimate reported for persons from other communities8,10,a estimate reported for persons from other communities12 Estimation with creatinine and race using existing equations but Estimation with cystatin, creatinine, and race using existing reporting without specification of race equations but reporting without specification of race (2) eGFRcr (CKD-EPI) (age, sex, race) with “Black” estimate reported as (14) eGFRcr-cys (CKD-EPI) (age, sex, race) with “Black” estimate “high muscle mass,” and “non-Black” estimate reported as “low reported as “high muscle mass,” and non-Black estimate reported muscle mass”a as “low muscle mass” (3) eGFRcr (CKD-EPI) (age, sex, race) with “Black” estimate reported as (15) eGFRcr-cys (CKD-EPI) (age, sex, race) with “Black” estimate “high value,” and “White” reported as “low value”a reported as “high value,” and “White” reported as “low value”a (4) eGFRcr (CKD-EPI) (age, sex, race) with the Black coefficient ignored (16) eGFRcr-cys (CKD-EPI) (age, sex, race) with the Black coefficient and eGFR value for White/other is reported for alla ignored and value for White/Other is reported for all (5) eGFRcr (CKD-EPI) (age, sex, race), with the Black coefficient used (17) eGFRcr-cys (CKD-EPI) (age, sex, race), with the Black coefficient and eGFR value for African Americans is reported for all used and value for African Americans is reported for all (6) Blended eGFRcr (CKD-EPI) (age, sex, race) using a single coefficient (18) Blended eGFRcr-cys (CKD-EPI) (age, sex, race) using a single weighted for percentage of African Americans in the specific coefficient weighted for percentage of African Americans in the population is reported for all specific population is reported for all Estimation with creatinine that do not include race Estimation with cystatin C only (7) CG estimated creatinine clearance (age, sex, weight)6,a,b (19) eGFRcys (CKD-EPI) (age, sex)76,a (8) eGFRcr (FAS) (age, sex)91 (20) eGFRcys (FAS) (age, sex)92 (9) eGFRcr (EKFC) (age, sex)93 (21) eGFRcys (CAPA) (age)94 (10) eGFR (LM) (age, sex)95 Equations to be developed to estimate GFR with creatinine that do Equations to be developed to estimate GFR with creatinine and not include race cystatin C that do not include race (11)eGFRcrrefit without race variable (22) eGFRcr-cys refit without race variable (12)eGFRcrrefit with height and weight without race variable Estimation with creatinine only that does not include race (23) eGFRcr-cys (FAS) (age, sex)92 Estimations with new filtration markers in combination with creatinine or cystatin C that do not include race (24)eGFRcys-b2m-btp (age, sex)96 (25) eGFRcr-cys-b2m-btp (age, sex)96 (26) Any of the above either in combination or in sequence with measured GFR using exogenous filtration markers or measured creatinine clearance, to be used generally or by clinical indication (e.g., donation, diagnosis, prescription, referral, transplant): Example: One of the above approaches followed by another approach for confirmation. Parentheses indicate coefficients included in the development of the equation. eGFRcr-cys, estimated GFR with creatinine and cystatin C; CG, Cockcroft–Gault; FAS, full age spectrum; EKFC, European Kidney Function Consortium; CAPA, Caucasian and Asian Pediatric and Adult; LM, Lund–Malmo; b2m, b2 microglobulin; btp, b-trace protein. aUsed or in use in at least one US setting. bCG creatinine clearance is reported in ml/min, eGFR results are standardized (or indexed) to a body surface area of 1.73 m2 and are reported in ml/min per 1.73 m2. and that a careful review of the evidence education and sustained efforts to kidney health and to eliminate health must guide its recommendations. The monitor and assure patient safety and disparities. task force also recognizes that alignment health equity. Assessing the inclusion of US clinical laboratories is critical to of race in estimating GFR is part of a maintain the success achieved over the larger conversation in addressing ra- DISCLOSURES past two decades in reporting of eGFR, cial disparities in kidney health. NKF, which has improved the quality of care ASN, and the task force encourage M. Baweja reports having interests/relationships for millions of Americans. the community of healthcare profes- with Physicians for Human Rights, Young Center NKF, ASN, and the task force ap- sionals, scientists, medical educa- for Immigrant Children’s Rights, and Premier, Inc. preciate that issuing recommenda- tors, students, health professionals in D.C. Crews reports serving on the Nephrology Board of the American Board of Internal Medi- tions is only the beginning of change. training, and patients to join in the cine, on the Council of Subspecialist Societies at Implementing recommendations of larger, comprehensive effort needed the American College of Physicians, on the Bayer this magnitude will require extensive to address the entire spectrum of HealthCare Pharmaceuticals Inc, Patient and

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Table 5. Sample of attributes to be considered in making a recommendation among alternative approaches to estimation of kidney function (eGFR) Attribute Filtration biomarker availability Input variable for computation (race, filtration biomarker, age, sex, body composition measure) Representation in development and validation of a diverse population with regard to race, ethnicity, sex, age, body composition, severity and cause of kidney disease, and socioeconomic status Bias compared with measured kidney function for different race and ethnic groups Accuracy compared with measured kidney function for different race and ethnic groups Consequences of equation used for clinical decisions with regard to evaluation and management of patients’ kidney function, including health disparities and bias Availability of input variables for reporting (race, filtration biomarker, age, sex, body composition measure) Feasibility of standardization across the United States Patient-centered perspectives on approaches

Physician Advisory Board Steering Committee for technical expert panel for Quality Insights Kidney Centers for Disease Control and Prevention, At- Disparities in CKD Project, on the editorial board Care Pilot project; serving as a scientific advisory lanta, Georgia. The findings and conclusions in this of CJASN and Journal of Renal Nutrition,asasso- board member of the NKF and ASN Task Force on report are those of the authors and do not neces- ciate editor for Kidney360 as cochair of Kidney360, EGFR and Race; and having consultancy agree- sarily represent the official position of the Centers and on the Board of Directors of the NKF of Mary- ments with Total Renal Care, Inc. N.R. Powe re- for Disease Control and Prevention. Because land/Delaware; receivingresearchfundingfrom ports serving as a JASN associate editor; reports Marva M. Moxey-Mims and Neil R. Powe are As- Somatus, Inc.; and having consultancy agreements receiving honoraria from the Patient Centered sociate Editors of JASN, they were not involved in with Yale New Haven Health Services Corporation Outcomes Research Institute, Robert Wood John- the peer review process for this manuscript. An- Center for Outcomes Research and Evaluation son Foundation, University of Washington, Yale other editor oversaw the peer review and decision- (CORE). C. Delgado reports her contribution is University, and Vanderbilt University; and serving making process for this manuscript. in part supported with the resources and the use as a scientific advisor for the Patient Centered Out- of facilities at the San Francisco VA Medical Center. comes Research Institute, Robert Wood Johnson N.D. Eneanya reports receiving honoraria from Foundation, University of Washington, Vanderbilt Columbia University Medical Center, Gerson University, and Yale University. G.V. Roberts re- SUPPLEMENTAL MATERIAL Lehrman, Harvard University, Partner’sHealth- ports serving on a speakers bureau with American care, Quality Insights, SCAN Healthcare, Univer- Association of Kidney Patients; receiving honoraria This article contains the following supplemental sity of California Irvine, and Wake Forest School of from APOLLO; serving on the APOLLO NIDDK material online at http://jasn.asnjournals.org/ Medicine; serving as a scientificadvisorfor, Study Community Advisory Committee, Can- lookup/suppl/doi:10.1681/ASN.2021010039/-/ or member of, Healthcare: The Journal of Delivery SOLVE CKD International Research Advisory Com- DCSupplemental. Science and Innovation and Kidney Medicine;and mittee, International Nephrology Society (ISN) Patient Supplemental Material 1. Topics and informants having consultancy agreements with Somatus. Group, University of Washington (UW) Center for during phase 2. C. Gadegbeku reports receiving research funding Dialysis Innovation Patient Advisory Board, and UW Supplemental Material 2. Terms and definitions. from Akebia and Vertex; serving as scientific advi- Kidney Research Institute Patient Advisory Commit- sor for, or member of, the ASN Council; and hav- tee; having other interests/relationships with the ASN ing consultancy agreements with Fresenius Kid- COVID-19 Response Team and Transplant Subcom- ney Care as medical director. L.A. Inker reports mittee and Kidney Health Initiative Patient and REFERENCES serving as scientific advisor or member of, Alport’s Family Partnership Council; serving as an advisory Foundation, Goldfinch, and Diametrix; member of committee member for Home Dialyzors United; 1. Miller WG, Jones GRD: Estimated glomerular the ASN and member of National Kidney Disease and having ownership interest in Microsoft. filtration rate; laboratory implementation and Education Program; having consultancy agree- C. 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12 JASN JASN 32: ccc–ccc,2021 www.jasn.org SPECIAL ARTICLE

86. Schwartz GJ, Muñoz A, Schneider MF, Mak 91. Pottel H, Hoste L, Dubourg L, Ebert N, assays standardized to the international cal- RH, Kaskel F, Warady BA, et al.: New equa- Schaeffner E, Eriksen BO, et al.: An estimated ibrator. Clin Chem 60: 974–986, 2014 tions to estimate GFR in children with CKD. glomerular filtration rate equation for the full 95. Björk J, Grubb A, Sterner G, Nyman U: Revised J Am Soc Nephrol 20: 629–637, 2009 age spectrum. Nephrol Dial Transplant 31: equations for estimating glomerular filtration 10.1681/ASN.2008030287 798–806, 2016 10.1093/ndt/gfv454 rate based on the Lund-Malmö Study cohort. 87. Weisz G, Cambrosio A, Keating P, Knaapen 92. Pottel H, Delanaye P, Schaeffner E, Dubourg Scand J Clin Lab Invest 71: 232–239, 2011 L, Schlich T, Tournay VJ: The emergence of L, Eriksen BO, Melsom T, et al.: Estimating 96. Inker LA, Couture SJ, Tighiouart H, Abraham clinical practice guidelines. Milbank Q 85: glomerular filtration rate for the full age AG, Beck GJ, Feldman HI, et al.; CKD-EPI 691–727, 2007 spectrum from serum creatinine and cystatin GFR Collaborators: A new panel estimated

88. Miller WG, Greenberg N: Harmonization and C. Nephrol Dial Transplant 32: 497–507, GFR, including b 2-microglobulin and b-trace standardization: Where are we now? JAppl 2017 10.1093/ndt/gfw425 protein and not including race, developed in Lab Med 6: 510–521, 2021 93. Pottel H, Bjork J, Courbebaisse M, Couzi L, Ebert a diverse population [published online 89. Miller WG, Tate JR, Barth JH, Jones GR: N, Eriksen BO, et al.: Development and valida- ahead of print December 4, 2020]. Am Harmonization: The sample, the measure- tion of a modified full age spectrum creatinine- J Kidney Dis 10.1053/j.ajkd.2020.11.005 ment, and the report. Ann Lab Med 34: based equation to estimate glomerular filtra- 97. What is patient-centered care? NEJM Catal 187–197, 2014 tion rate: A cross-sectional analysis of pooled 3: 2017 90. Peek ME, Tang H, Cargill A, Chin MH: Are data. Ann Intern Med 174: 183–191, 2021 there racial differences in patients’ shared 94. Grubb A, Horio M, Hansson L-O, Björk J, decision-making preferences and behaviors Nyman U, Flodin M, et al.: Generation of a among patients with diabetes? Med Decis new cystatin C-based estimating equation See related editorial, “Race and the Estimation of Making 31: 422–431, 2011 for glomerular filtration rate by use of 7 GFR: Getting it Right,” on pages XXX–XXX.

AFFILIATIONS

1Nephrology Section, San Francisco Veterans Affairs Medical Center, Division of Nephrology, University of California San Francisco, San Francisco, California 2Nephrology Division, Department of Medicine, Translational Transplant Research Center, Icahn School of Medicine at Mount Sinai, New York, New York 3Division of Diabetes Translation, Centers for Disease Control and Prevention, Atlanta, Georgia 4Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 5Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 6Department of Medicine, Section of Nephrology, Hypertension and Kidney Transplantation, Temple University, Philadelphia, Pennsylvania 7Division of Nephrology, Tufts Medical Center, Boston, Massachusetts 8Division of Renal Medicine and Office of the Chief Medical Officer, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 9Department of Pathology, Virginia Commonwealth University, Richmond, Virginia 10Division of Nephrology, Children’s National Hospital, Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC 11External Relations and Patient Engagement, Kidney Research Institute, Center for Dialysis Innovation, University of Washington, Seattle, Washington 12College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 13National Kidney Foundation, New York, New York 14Department of Medicine, Priscilla Chan and Mark Zuckerberg San Francisco General Hospital, University of California San Francisco, San Francisco, California

JASN 32: ccc–ccc, 2021 Reassessing Race in eGFR 13 Supplemental Table of Contents

Supplemental Material 1: Topics and Informants During Phase Two Supplemental Material 2: Terms and Definitions

Supplemental Material 1

Topics and Informants During Phase Two Topic Moderators and Panelists/Discussants Location Transplant Waitlist and Neil Powe, MD, MPH, MBA Nephrology Referral and Winfred Williams, MD Boston, MA Kidney Donation Evaluation Delphine Tuot, MD San Francisco, CA Vineeta Kumar, MD Birmingham, AL Tanjala Purnell, PhD Baltimore, MD Elaine Ku, MD San Francisco,CA Michelle Josephson, MD Chicago, IL Silas Norman, MD Ann Arbor, MI Quantifying Impact of Race Nwamaka Eneanya, MD, MPH; Mallika Mendu, MD, MBA Removal and Patient Safety Arjun Manrai, MD Boston, MA Considerations Salman Ahmed, MD Boston, MA Melanie Hoenig, MD Boston, MA Rajnish Mehrotra, MD Seattle, WA Alp Ikizler, MD, PhD Nashville, TN Jeffrey Fink, PhD Baltimore, MD Karthik Sivashanker, MD Boston, MA Alan Kliger, MD New Haven, CT Lee-Ann Wagner, MD Baltimore, MD Tom Sequist, MD Boston, MA The role of eGFR on Wendy St. Peter, PharmD; Mallika Mendu, MD, MBA Pharmacologic Amit Pai, PharmD Ann Arbor, MN Considerations Erin F. Barretto, PharmD, RPH Rochester, MN Joanna Hudson, PharmD Nashville, TN Paul Palevsky, MD Pittsburgh, PA James Wetmore, MD, MS Minneapolis, MN Thomas Nolin, PharmD, PhD Pittsburgh, PA Jeffrey Fink, PhD Baltimore, MD Silvia Titan, MD, PhD Boston, MA Katherine Tuttle, MD Spokane, WA Michael Shlipak, MD San Francisco, CA Minority Participation in Crystal Gadegbeku, MD; Marva M. Moxey-Mims, MD Clinical Trials and CKD David M. Charytan, MD New York, NY Research in African Jackson T. Wright, MD, PhD Cleveland, OH Americans Herman A. Taylor, Jr., MD Atlanta, GA Keith C. Norris, MD Los Angeles, CA L. Ebony Boulware, MD, MPH Durham, NC Stephen B. Thomas, MS, PhD College Park, MD Akinlolu O. Ojo, MD, PhD, MBA, MPH Kansas City, KS The Food and Drug Wendy St. Peter, PharmD; Nilka Rios Burrows, MPH, MT Administration, Centers for Thomas Nolin, PharmD, PhD Pittsburgh, PA Medicare and Medicaid Aliza Thompson, MD, MS Silver Spring, MD Services perspectives on Julia Breyer Lewis, MD Nashville, TN Drug Approval and Afshin Parsa, MD, MPH Baltimore, MD Population Tracking Morgan Grams, MD, PhD, MHS Baltimore, MD Joseph Coresh, MD, PhD, MHS Baltimore, MD Rajiv Saran, MBBS, MD, DTCD, MS Ann Arbor, MI Jessie Roach, MD Washington, DC Kirsten Johansen, MD Minneapolis, MN Sankar Naveneethan, MD, MS, MPH Houston, TX Susan Crowley, MD MBA West Haven, CT

Supplemental Material 2

Equity, Disparities, Health and Healthcare Term Definition Health Equity A fair and just opportunity to be as healthy as possible; Requiring the removal of obstacles to health, such as poverty, discrimination, and their consequences, including powerlessness and lack of access to good jobs with fair pay, quality education and housing, safe environments, and healthcare. For the purposes of measurement, health equity means reducing and ultimately eliminating disparities in health and its determinants that adversely affect excluded or marginalized groups. 1 Health Disparity A difference in the incidence, prevalence, mortality, and burden of disease and other adverse health conditions that exist among specific population groups in the United States. 2

Healthcare Differences between groups in health insurance Disparities coverage, access to and use of care, and quality of care. Health and healthcare disparities often refer to differences that are not explained by variations in health needs, patient preferences, or treatment recommendations and are closely linked with social, economic, and/or environmental disadvantage. 3

Race and Racism Race A construct of human variability based on perceived differences in biology, physical appearance and behavior but not a biological reality. 4 Racism An organized system, rooted in an ideology of inferiority that categorizes, ranks and differentially allocates societal resources to human population groups.5 Discrimination Differential actions toward others according to race. 6 Genetic Sets of polymorphisms for a particular DNA Ancestry sequence, identified as ancestry-informative markers, that appear in substantially different frequencies between populations from different geographical regions of the world that can be used to estimate the geographical origins of the ancestors of an individual typically by continent of origin (Africa, Asia, or Europe). 7 eGFR Evaluation Criterion Metric Definition Bias Median Median mGFR minus eGFR (closer to 0 is difference better)

Precision Interquartile IQR of mGFR minus eGFR (lower is better) range (IQR) of differences

Accuracy P30 Percentage of mGFR minus eGFR more than 30% of mGFR (varies from 0 to 100, higher is better) 1-P30 Percentage of mGFR minus eGFR less than 30% of mGFR (varies from 0 to 100, lower is better) Root mean Square root of the mean of square of log mGFR square error minus log eGFR (varies from 0 to 1, lower is (RMSE) better) Concordance Measure of agreement of eGFR vs. mGFR correlation along the identity line (varies from -1 to 1, coefficient (CCC) higher is better) Classification Concordance Percent of people with agreement in eGFR and mGFR category (varies from 0 to 100, higher is better) Reclassification Net Percent of correct reclassifications minus reclassification percent of incorrect reclassifications in people index (NRI) with disease plus percent of correct reclassifications minus percent of incorrect reclassifications in people without disease (varies from -200 to 200, higher is better) eGFR The use of an equation to numerically derives Computation an estimate of GFR eGFR Manner by which eGFR computed values are Reporting reported by clinical laboratories. Bias is 0 in development datasets. Measures of accuracy reflect precision when bias is 0. For these metrics, measures of bias, precision, classification, reclassification, and P30 are computed on the raw scale. RMSE, CCC, TDI 90 and CP 30 are computed on the log scale.

Table References

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