A Unifying Approach for GFR Estimation: Recommendations of the NKF-ASN Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease

BackgroundIn response to a national call for re-evaluation of the use of race in clinical algorithms, the National Kidney Foundation (NKF) and the American Society of Nephrology (ASN) established a Task Force to reassess inclusion of race in the estimation of glomerular filtration rate (GFR) in the United States and its implications for diagnosis and management of patients with, or at risk for, kidney diseases.Process & DeliberationsThe Task Force organized its activities over 10 months in phases to (1) clarify the problem and evidence regarding GFR estimating equations in the United States (described previously in an interim report), and, in this final report, (2) evaluate approaches to address use of race in GFR estimation, and (3) provide recommendations. We identified 26 approaches for the estimation of GFR that did or did not consider race and narrowed our focus, by consensus, to 5 of those approaches. We holistically evaluated each approach considering 6 attributes: assay availability and standardization; implementation; population diversity in equation development; performance compared with measured GFR; consequences to clinical care, population tracking, and research; and patient centeredness. To arrive at a unifying approach to estimate GFR, we integrated information and evidence from many sources in assessing strengths and weaknesses in attributes for each approach, recognizing the number of Black and non-Black adults affected.Recommendations(1) For US adults (>85% of whom have normal kidney function), we recommend immediate implementation of the CKD-EPI creatinine equation refit without the race variable in all laboratories in the United States because it does not include race in the calculation and reporting, included diversity in its development, is immediately available to all laboratories in the United States, and has acceptable performance characteristics and potential consequences that do not disproportionately affect any one group of individuals. (2) We recommend national efforts to facilitate increased, routine, and timely use of cystatin C, especially to confirm estimated GFR in adults who are at risk for or have chronic kidney disease, because combining filtration markers (creatinine and cystatin C) is more accurate and would support better clinical decisions than either marker alone. If ongoing evidence supports acceptable performance, the CKD-EPI eGFR–cystatin C (eGFRcys) and eGFR creatinine–cystatin C (eGFRcr-cys_R) refit without the race variables should be adopted to provide another first-line test, in addition to confirmatory testing. (3) Research on GFR estimation with new endogenous filtration markers and on interventions to eliminate race and ethnic disparities should be encouraged and funded. An investment in science is needed for newer approaches that generate accurate, unbiased, and precise GFR measurement and estimation without the inclusion of race, and that promote health equity and do not generate disparate care.ImplementationThis unified approach, without specification of race, should be adopted across the United States. High-priority and multistakeholder efforts should implement this solution. In response to a national call for re-evaluation of the use of race in clinical algorithms, the National Kidney Foundation (NKF) and the American Society of Nephrology (ASN) established a Task Force to reassess inclusion of race in the estimation of glomerular filtration rate (GFR) in the United States and its implications for diagnosis and management of patients with, or at risk for, kidney diseases. The Task Force organized its activities over 10 months in phases to (1) clarify the problem and evidence regarding GFR estimating equations in the United States (described previously in an interim report), and, in this final report, (2) evaluate approaches to address use of race in GFR estimation, and (3) provide recommendations. We identified 26 approaches for the estimation of GFR that did or did not consider race and narrowed our focus, by consensus, to 5 of those approaches. We holistically evaluated each approach considering 6 attributes: assay availability and standardization; implementation; population diversity in equation development; performance compared with measured GFR; consequences to clinical care, population tracking, and research; and patient centeredness. To arrive at a unifying approach to estimate GFR, we integrated information and evidence from many sources in assessing strengths and weaknesses in attributes for each approach, recognizing the number of Black and non-Black adults affected. (1) For US adults (>85% of whom have normal kidney function), we recommend immediate implementation of the CKD-EPI creatinine equation refit without the race variable in all laboratories in the United States because it does not include race in the calculation and reporting, included diversity in its development, is immediately available to all laboratories in the United States, and has acceptable performance characteristics and potential consequences that do not disproportionately affect any one group of individuals. (2) We recommend national efforts to facilitate increased, routine, and timely use of cystatin C, especially to confirm estimated GFR in adults who are at risk for or have chronic kidney disease, because combining filtration markers (creatinine and cystatin C) is more accurate and would support better clinical decisions than either marker alone. If ongoing evidence supports acceptable performance, the CKD-EPI eGFR–cystatin C (eGFRcys) and eGFR creatinine–cystatin C (eGFRcr-cys_R) refit without the race variables should be adopted to provide another first-line test, in addition to confirmatory testing. (3) Research on GFR estimation with new endogenous filtration markers and on interventions to eliminate race and ethnic disparities should be encouraged and funded. An investment in science is needed for newer approaches that generate accurate, unbiased, and precise GFR measurement and estimation without the inclusion of race, and that promote health equity and do not generate disparate care. This unified approach, without specification of race, should be adopted across the United States. High-priority and multistakeholder efforts should implement this solution. Plain-Language SummaryA Task Force from the National Kidney Foundation and American Society of Nephrology developed recommendations for reassessing inclusion of race in the estimation of glomerular filtration rate (GFR) in the United States. The Task Force recommends immediate implementation of the Chronic Kidney Disease Epidemiology Collaboration creatinine equation refit without the race variable in all laboratories because the calculation does not include race, it included diversity in its development, its potential adverse consequences do not disproportionately affect any one group, and it is immediately available to all laboratories. A second recommendation calls for national efforts to facilitate increased, routine, and timely use of cystatin C, especially to confirm estimated GFR in adults for clinical decision making. A third recommendation encourages research on GFR estimation with new endogenous filtration markers and interventions to eliminate racial and ethnic disparities.Editorial, p. 153 A Task Force from the National Kidney Foundation and American Society of Nephrology developed recommendations for reassessing inclusion of race in the estimation of glomerular filtration rate (GFR) in the United States. The Task Force recommends immediate implementation of the Chronic Kidney Disease Epidemiology Collaboration creatinine equation refit without the race variable in all laboratories because the calculation does not include race, it included diversity in its development, its potential adverse consequences do not disproportionately affect any one group, and it is immediately available to all laboratories. A second recommendation calls for national efforts to facilitate increased, routine, and timely use of cystatin C, especially to confirm estimated GFR in adults for clinical decision making. A third recommendation encourages research on GFR estimation with new endogenous filtration markers and interventions to eliminate racial and ethnic disparities. Editorial, p. 153 On July 2, 2020 the National Kidney Foundation (NKF) and the American Society of Nephrology (ASN) announced they would establish a Task Force to reassess the inclusion of race in the estimation of glomerular filtration rate (GFR) in the United States and its implications for diagnosis and management of patients with, or at risk for, kidney diseases. The rationale for the Task Force includes the following: race is a social and not a biological construct, the problematic nature of applying race to clinical algorithms, and the need to advance health equity and social justice. These factors have been described.1Delgado C. Baweja M. Burrows N.R. et al.Reassessing the Inclusion of Race in Diagnosing Kidney Diseases: An Interim Report From the NKF-ASN Task Force.Am J Kidney Dis. 2021; 78: 103-115Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar The Task Force organized its activities in 3 phases: (1) clarify the problem and evidence regarding GFR estimating equations in the United States, (2) evaluate approaches to address the use of race in GFR estimation, and (3) provide recommendations.1Delgado C. Baweja M. Burrows N.R. et al.Reassessing the Inclusion of Race in Diagnosing Kidney Diseases: An Interim Report From the NKF-ASN Task Force.Am J Kidney Dis. 2021; 78: 103-115Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar The Task Force published an interim report that detailed phase 1, described the nearly 50-year evolution of estimating equations, and included scientific evidence and values held by members.1Delgado C. Baweja M. Burrows N.R. et al.Reassessing the Inclusion of Race in Diagnosing Kidney Diseases: An Interim Report From the NKF-ASN Task Force.Am J Kidney Dis. 2021; 78: 103-115Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar In this final report, we outline a path forward in GFR estimation that integrates filtration marker/assay availability and standardization, implementation challenges, equation derivation population diversity, equation performance, avoidance of foreseeable adverse clinical consequences, and patient centeredness. In alignment with the NKF and ASN, the Task Force unanimously agreed that race should be removed from estimating equation calculation and reporting. Thus, the Task Force used a comprehensive process of evidence ascertainment to identify the most patient-centered solution that did not include race (Fig 1). The Task Force sought to have an inclusive, comprehensive, and in-depth process that, after establishment of the Task Force, took 10 months (September 2020 to June 2021). This final report describes the multiple sources (expert testimony; new social and scientific evidence; oral testimonies from patients, providers, and trainees; and community feedback on the interim report) used to gather information, describes the information assembled on 26 approaches and evaluates their attributes, and explains how we integrated this information into a unifying solution. The Task Force conducted >40 sessions to assemble and review the data and evidence, including extensive expert testimony. In the 16 sessions that heard testimony, covering a broad range of related topics, 97 experts presented a diversity of views, representing 21 US states and 7 other countries.1Delgado C. Baweja M. Burrows N.R. et al.Reassessing the Inclusion of Race in Diagnosing Kidney Diseases: An Interim Report From the NKF-ASN Task Force.Am J Kidney Dis. 2021; 78: 103-115Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar The Task Force constructed statements of evidence and value, established criteria to evaluate approaches (in the interim report), and identified 26 potential approaches for GFR estimation that were available or in development, with an option to combine approaches according to clinical indication (Table 1, Table S1). The Task Force gathered additional community input in recognition of differing views, and information regarding nascent science.Table 1Inventory of Possible Approaches to Estimating and Reporting GFR, Attributes, and ChallengesApproachAcronymRace IncludedaRace included in calculation (C) or reporting (R) of equation.Challenges by AttributebDetails of origin of attributes in Delgado et al.1 Details on basis for categorization in Items S1-S3. Attributes are labeled as follows: 1, filtration marker assay; 2, implementation challenges; 3, equation population diversity; 4, equation performance; 5, consequences; 6, patient centeredness. For the difficulties assessment, green represents minimal challenges, yellow represents some challenges, and purple represents many challenges; mixed yellow/purple represents no consensus among Task Force members between some and many challenges.123456Creatinine used as biomarker1. CKD-EPI eGFRcr (age, sex, race)6Levey A.S. Stevens L.A. Schmid C.H. Zhang Y.L. Castro 3rd, A.F. Feldman H.I. et al.CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration): A new equation to estimate glomerular filtration rate.Ann Intern Med. 2009; 150: 604-612Crossref PubMed Scopus (14386) Google ScholarCKD-EPIcr✓CR2. MDRD Study (age, sex, race)7Levey A.S. Bosch J.P. Lewis J.B. Greene T. Rogers N. Roth D. Modification of Diet in Renal Disease Study Group: A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation.Ann Intern Med. 1999; 130: 461-470Crossref PubMed Scopus (12682) Google ScholarMDRDcr✓CR3. eGFRcr (CKD-EPI) (age, sex, race) with “Black” estimate reported as “high muscle mass” and non-Black estimate reported as “low muscle mass”CKD-EPIcr_MM✓C4. eGFRcr (CKD-EPI) (age, sex, race) with “Black” estimate reported as “high value” and non-Black reported as “low value”CKD-EPIcr_H/L✓C5. eGFRcr (CKD-EPI) (age, sex, race) with the Black coefficient removed and eGFR value for non-Black reported for allCKD-EPIcr_NB✓C6. eGFRcr (CKD-EPI) (age, sex, race), with the Black coefficient used and eGFR value for Black individuals reported for allCKD-EPIcr_B✓C7. Blended eGFRcr (CKD-EPI) (age, sex, race), using single coefficient weighted for percentage of Black individuals in specific population, reported for allCKD-EPIcr_blend✓C8. CG estimated creatinine clearance (age, sex, weight)8Cockcroft D.W. Gault M.H. Prediction of creatinine clearance from serum creatinine.Nephron. 1976; 16: 31-41Crossref PubMed Scopus (12826) Google ScholarCG_Clcr9. eGFRcr (FAS) (age, sex, population-specific Scr/Q)43Pottel H. Hoste L. Dubourg L. Ebert N. Schaeffner E. Eriksen B.O. et al.An estimated glomerular filtration rate equation for the full age spectrum.Nephrol Dial Transplant. 2016; 31: 798-806Crossref PubMed Scopus (237) Google ScholarFAScr10. eGFRcr (EKFC) (age, sex, population-specific Scr/Q)27Pottel H. Bjork J. Courbebaisse M. Couzi L. Ebert N. Eriksen B.O. et al.Development and validation of a modified full age spectrum creatinine-based equation to estimate glomerular filtration rate: A cross-sectional analysis of pooled data.Ann Intern Med. 2021; 174: 183-191Crossref PubMed Scopus (42) Google ScholarEKFCcr11. eGFR (LM) (age, sex)44Bjork J. Grubb A. Sterner G. Nyman U. Revised equations for estimating glomerular filtration rate based on the Lund-Malmo Study cohort.Scand J Clin Lab Invest. 2011; 71: 232-239Crossref PubMed Scopus (117) Google ScholarLMcr12. eGFRcr (CKD-EPI) refit without race variable38Inker L.A. Eneanya N.D. Coresh J. et al.Chronic Kidney Disease Epidemiology Collaboration. New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race. N Engl J Med. Published online September 23, 2021.doi:10.1056/NEJMoa2102953Google ScholarCKD-EPIcr_R13. eGFRcr (CKD-EPI) refit with height and weight without race variable45Levey A.S. Tighiouart H. Titan S.M. Inker L.A. Estimation of glomerular filtration rate with vs without including patient race.JAMA Intern Med. 2020; 180: 793-795Crossref PubMed Scopus (33) Google ScholarCKD-EPI_R_HWCreatinine in combination with cystatin C or other markers14. eGFRcr-cys (CKD-EPI) with race coefficient (age, sex, race)46Inker L.A. Schmid C.H. Tighiouart H. Eck- feldt J.H. Feldman H.I. Greene T. et al.CKD-EPI Investigators: Estimating glomerular filtration rate from serum creatinine and cystatin C.N Engl J Med. 2012; 367: 20-29Crossref PubMed Scopus (2246) Google ScholarCKD-EPIcr-cys✓CR15. eGFRcr-cys (CKD-EPI) (age, sex, race) with “Black” estimate reported as “high muscle mass” and non-Black estimate reported as “low muscle mass”CKD-EPIcr-cys_MM✓C16. eGFRcr-cys (CKD-EPI) (age, sex, race) with “Black” estimate reported as “high value” and non-Black estimate reported as “low value”CKD-EPIcr-cys_H/L✓C17. eGFRcr-cys (CKD-EPI) (age, sex, race) with the Black coefficient removed and value for non-Black estimate reported for allCKD-EPIcr-cys_NB✓C18. eGFRcr-cys (CKD-EPI) (age, sex, race) with Black coefficient used and value for Black individuals reported for allCKD-EPIcr-cys_B✓C19. Blended eGFRcr-cys (CKD-EPI) (age, sex, race), using a single coefficient weighted for percentage of Black patients in the specific population, reported for allCKD-EPIcr-cys_blend✓C20. eGFRcr-cys (CKD-EPI) refit without race variable38Inker L.A. Eneanya N.D. Coresh J. et al.Chronic Kidney Disease Epidemiology Collaboration. New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race. N Engl J Med. Published online September 23, 2021.doi:10.1056/NEJMoa2102953Google ScholarCKD-EPIcr-cys_R21. eGFRcr-cys (FAS) (age, sex, population-specific Q)47Pottel H. Delanaye P. Schaeffner E. Dubourg L. Eriksen B.O. Melsom T. et al.Estimating glomerular filtration rate for the full age spectrum from serum creatinine and cystatin C.Nephrol Dial Transplant. 2017; 32: 497-507PubMed Google ScholarFAScr-cys22. eGFRcr-cys-B2M-BTP (age, sex)48Inker L.A. Couture S.J. Tighiouart H. Abraham A.G. Beck G.J. Feldman H.I. et al.CKD-EPI GFR CollaboratorsA new panel- estimated GFR, including β2-microglobulin and β-trace protein and not including race, developed in a diverse population.Am J Kidney Dis. 2021; 77: 673-683.e1Abstract Full Text Full Text PDF PubMed Scopus (21) Google ScholarCKD-EPI_4MCystatin C or other filtration markers23. eGFRcys (CKD-EPI) (age, sex)49Inker L.A. Eckfeldt J. Levey A.S. Leien- decker-Foster C. Rynders G. Manzi J. et al.Expressing the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) cystatin C equations for estimating GFR with standardized serum cystatin C values.Am J Kidney Dis. 2011; 58: 682-684Abstract Full Text Full Text PDF PubMed Scopus (154) Google ScholarCKD-EPIcys24. eGFRcys (FAS) (age, sex, population-specific Q)47Pottel H. Delanaye P. Schaeffner E. Dubourg L. Eriksen B.O. Melsom T. et al.Estimating glomerular filtration rate for the full age spectrum from serum creatinine and cystatin C.Nephrol Dial Transplant. 2017; 32: 497-507PubMed Google ScholarFAScys25. eGFRcys (CAPA) (age, sex)50Grubb A. Horio M. Hansson L.-O. Bjork J. Nyman U. Flodin M. et al.Generation of a new cystatin C-based estimating equation for glomerular filtration rate by use of 7 assays standardized to the international calibrator.Clin Chem. 2014; 60: 974-986Crossref PubMed Scopus (175) Google ScholarCAPAcys26. eGFRcys-B2M-BTP (age, sex)48Inker L.A. Couture S.J. Tighiouart H. Abraham A.G. Beck G.J. Feldman H.I. et al.CKD-EPI GFR CollaboratorsA new panel- estimated GFR, including β2-microglobulin and β-trace protein and not including race, developed in a diverse population.Am J Kidney Dis. 2021; 77: 673-683.e1Abstract Full Text Full Text PDF PubMed Scopus (21) Google ScholarCKD-EPI_3MAbbreviations: B2M, β2-microglobulin; BTP, β-trace protein; CAPA, Caucasian, Asian, pediatric, and adult; CG, Cockcroft and Gault; eGFRcr, eGFR computed using creatinine; eGFRcr-cys, eGFR computed using creatinine and cystatin C; eGFRcys, eGFR computed with cystatin C; EKFC, European Kidney Function Consortium; FAS, full age spectrum; LM, Lund-Malmo; Q, Q factor coefficient; Scr, serum creatinine.a Race included in calculation (C) or reporting (R) of equation.b Details of origin of attributes in Delgado et al.1Delgado C. Baweja M. Burrows N.R. et al.Reassessing the Inclusion of Race in Diagnosing Kidney Diseases: An Interim Report From the NKF-ASN Task Force.Am J Kidney Dis. 2021; 78: 103-115Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar Details on basis for categorization in Items S1-S3. Attributes are labeled as follows: 1, filtration marker assay; 2, implementation challenges; 3, equation population diversity; 4, equation performance; 5, consequences; 6, patient centeredness. For the difficulties assessment, green represents minimal challenges, yellow represents some challenges, and purple represents many challenges; mixed yellow/purple represents no consensus among Task Force members between some and many challenges. Open table in a new tab Abbreviations: B2M, β2-microglobulin; BTP, β-trace protein; CAPA, Caucasian, Asian, pediatric, and adult; CG, Cockcroft and Gault; eGFRcr, eGFR computed using creatinine; eGFRcr-cys, eGFR computed using creatinine and cystatin C; eGFRcys, eGFR computed with cystatin C; EKFC, European Kidney Function Consortium; FAS, full age spectrum; LM, Lund-Malmo; Q, Q factor coefficient; Scr, serum creatinine. The Task Force sought input from the community at large regarding the effect of particular approaches on clinical outcomes and health equity, through written and oral testimony, in separate web-based forums for (1) students and trainees; (2) clinicians, scientists, and other allied health professionals; and (3) patients, family members, and other public stakeholders (450 individuals from 18 states and 3 countries). The testimony addressed the limitations of GFR estimating equations and the importance of considering the potential role of including race in GFR estimating equations in perpetuating or preventing health care disparities. Trainees, patients, and health care professionals were unified in their desire to promote equity in health and health care delivery. The Task Force called for research from the scientific community on innovative solutions in estimating equations and in assessing kidney function. Sixteen investigators, nationally and globally, provided new information on kidney function measurement, accuracy of estimating equations, and biomarkers without a race variable (Table S2). National Institutes of Health (NIH) program leaders also provided commentary. A solution based upon the possible identified approaches would ideally promote racial equity and have the previously noted desirable attributes (Figure 1). Task Force members divided into attribute-defined subgroups, on the basis of their expertise, to examine in detail how each of the 26 GFR estimation approaches aligned with each desired attribute (Table 1). Each attribute subgroup presented its findings over several weeks to the entire Task Force for review and discussion. After review and discussion of each attribute independently, it was clear to the Task Force that not all approaches were viable in the short or intermediate time frame, and that the consequences for decision making and racial disparities in general medical care, medication use, nephrology care, and clinical trial eligibility and recruitment for some approaches were complex. The Task Force recognized that attributes can be inter-related and influence each other. As such, the Task Force eliminated, by consensus, some of the 26 approaches from further consideration. The decisions were not made on the basis of any single identified limitation but considered multiple independently identified difficulties, including the use of race in equation calculations or in reporting (Table 1). For example, equations that include novel filtration markers would be less likely to have standardized assays across laboratories and less likely to be available on multiplex analyzers in all laboratories, leading to challenges in implementation by most clinical laboratories. This, in turn, would diminish uptake of such an approach, including for population tracking. The Task Force selected 5 approaches after extensive discussion of inter-relationships and paying attention to projected time frames to overcome any perceived limitation. However, the Task Force did review information on all 26 approaches for completeness. Leaders in the NKF and ASN with expertise in health equity, health care justice, quality of patient care, research, policy, and advocacy reviewed the final recommendations of the Task Force. Attribute information on the 5 selected approaches are shown in Table 1, Table 2, Table 3, Table 4, Table 5, Table 6 and Figure 2, Figure 3, and for all approaches in Tables S3-S7.Table 2Attributes 1-4 Summary: Filtration Marker Assay, Implementation Challenges, Equation Marker, Performance Compared With mGFR AssayApproachesAttribute 1: AssayAttribute 2: ImplementationAttribute 3: Equation Derivation Population DiversityAttribute 4: Performance in External Validation for Black AdultsaND indicates there was no difference in performance compared with approach 1 (CKD-EPIcr), as indicated by nonoverlapping confidence intervals for performance. We evaluated the absolute magnitude of the bias. If the direction of the bias changed but the absolute magnitude was the same, this is indicated with an asterisk (∗). If a difference was observed, then the magnitude of the bias or inaccuracy is indicated by the number of arrows. Down arrow indicates worse performance and up arrow indicates better performance compared with approach CKD-EPIcr. For details, see Item S1 and Tables S3-S4. For bias, small, medium, and large are defined as the median difference between mGFR and eGFR of 0 to±5, ±5 to±10, and more than±10mL/min/1.73m2. For differential bias, small, medium, and large are defined as difference in bias between Black and non-Black individuals of<2.5, 2.6-5, and>5mL/min/1.73m2. For accuracy, small, medium, and large is indicated as percentage of estimates>30% of mGFR (1 – P30) of 10%, 10%-20%, and>20%. See Table S3 for other approaches.AvailabilityStandardizedHigh-Volume ThroughputLabsClinical PracticeBiasDifferential BiasAccuracy1. CKD-EPIcrWYYIn current useRACDGReferenceReferenceReference5. CKD-EPI_NBWYYCRNPRACDG↓↓↓↓↓ND12. CKD-EPIcr_RWYYCENPRACDGND∗↓↓↓ND17. CKD-EPIcr-cys_NBSYNNFNPRACDGND∗↓↑20. CKD-EPIcr-cys_RSYNCE, NFNPRACDG↑↓↑23. CKD-EPIcysSYNNC, NFNPRACDG↑NDNDSee Table 1 for details on listed approaches; Tables S3-S4 provides attributes for all approaches. Abbreviations: CE, change to equation; CR, change to reporting only; Lab, laboratory; N, no; ND, no difference (see footnote below); NF, new filtration marker; NP, no problems anticipated; RACDG, race groups–age–chronic kidney disease status–diabetes status–gender; S, specialized labs; W, widespread; Y, yes.a ND indicates there was no difference in performance compared with approach 1 (CKD-EPIcr), as indicated by nonoverlapping confidence intervals for performance. We evaluated the absolute magnitude of the bias. If the direction of the bias changed but the absolute magnitude was the same, this is indicated with an asterisk (∗). If a difference was observed, then the magnitude of the bias or inaccuracy is indicated by the number of arrows. Down arrow indicates worse performance and up arrow indicates better performance compared with approach CKD-EPIcr. For details, see Item S1 and Tables S3-S4. For bias, small, medium, and large are defined as the median difference between mGFR and eGFR of 0 to ±5, ±5 to ±10, and more than ±10 mL/min/1.73 m2. For differential bias, small, medium, and large are defined as difference in bias between Black and non-Black individuals of <2.5, 2.6-5, and >5 mL/min/1.73 m2. For accuracy, small, medium, and large is indicated as percentage of estimates >30% of mGFR (1 – P30) of 10%, 10%-20%, and >20%. See Table S3 for other approaches. Open table in a new tab Table 3Possible Consequences of Approaches for Clinical Decision Making (Attribute 5): General Medical Care Evaluation and ManagementApproachImplicationsGeneral Medical CareRiskCKD Screening or Detection (eGFR < 60)aCKD defined as GFR<60mL/min/1.73m2 or presence of kidney damage for at least 3 months. For this table, we are using only a one-time assessment of GFR<60mL/min/1.73m2 to isolate the effect of new GFR equations on CKD prevalence.Nephrology Referral (eGFR < 30)Radiographic Diagnostic Assessment (eGFR < 30)MortalityKidney Failure With Replacement TherapyIncident CKD (eGFR > 60)1. CKD-EPIcrNo. of Black adults meeting thresholdbAII values approximate and based on combination of reports using simulations of NHANES or clinical datasets.22-26,38 This might not indicate what occurs in practice and cannot incorporate health care professional or patient behavior.1-2.1MbAII values approximate and based on combination of reports using simulations of NHANES or clinical datasets.22-26,38 This might not indicate what occurs in practice and cannot incorporate health care professional or patient behavior.0.1-0.6M0.0-0.6M31M at riskcEstimated no. of Black adults living in the United States from 2019 US Census.31M at riskcEstimated no. of Black adults living in the United States from 2019 US Census.27M at riskdEstimated no. of Black adults with GFR>60mL/min/1.73m2 living in the United States; calculated by multiplying no. of Black adults from the 2019 census by the portion without CKD, as defined by GFR<60mL/min/1.73m2 and albuminuria from NHANES data.385. CKD-EPIcr_NBΔ in Black adults meeting threshold↑ 1-2M↑ ∼0.12M↑ ∼0.12MNQNQ↑ >2MPossib