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Estimation of Black-White Disparities in CKD Outcomes: Comparison Using the 2021 Versus the 2009 CKD-EPI Creatinine Equations

Published:January 07, 2022DOI:https://doi.org/10.1053/j.ajkd.2021.12.004
      To the Editor:
      Estimated glomerular filtration rate (eGFR) has been commonly used as a measure of kidney function in clinical practice and research. The widely used Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation has used sex, age, race (Black or non-Black), and serum creatinine to calculate eGFR, assigning a 16% higher eGFR for individuals identified as Black despite the same age, sex and serum creatinine.

      Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604-612. doi:150/9/604 [pii]

      Because race is a social, non-biologic construct,
      • Vyas D.A.
      • Eisenstein L.G.
      • Jones D.S.
      Hidden in Plain Sight - Reconsidering the Use of Race Correction in Clinical Algorithms.
      ,
      • Delgado 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.
      to provide a unifying approach for GFR estimation,
      • Delgado 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.
      a new CKD-EPI creatinine equation that does not use the race variable was recently developed
      • Inker L.A.
      • Eneanya N.D.
      • Coresh J.
      • et al.
      New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race.
      and is currently recommended by the National Kidney Foundation and American Society of Nephrology Task Force for U.S. adults.
      • Delgado C.
      • Baweja M.
      • Crews D.C.
      • et al.
      A Unifying Approach for GFR Estimation: Recommendations of the NKF-ASN Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease.
      ,
      • Delgado C.
      • Baweja M.
      • Crews D.C.
      • et al.
      A Unifying Approach for GFR Estimation: Recommendations of the NKF-ASN Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease.
      To understand the potential impact of the new equation on estimating racial disparities in clinical outcomes, we assessed the Black-White disparities in kidney replacement therapy (KRT) and death as outcomes after incident CKD defined using the 2009 and 2021 CKD-EPI creatinine equations. Our hypothesis is that the 2021 CKD-EPI equation developed without using the race variable would reduce estimates of racial disparities in CKD outcomes.
      The US Veterans Health Administration (VHA) provided a single source population from which veterans, either non-Hispanic White or non-Hispanic Black, were determined to have incident CKD stage G3 or higher based on outpatient serum creatinine using two alternative equations: (1) using the 2009 CKD-EPI with its race term included

      Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604-612. doi:150/9/604 [pii]

      (2009-CKD-EPI) to construct one cohort; and (2) using the 2021 CKD-EPI equation developed without the race variable
      • Inker L.A.
      • Eneanya N.D.
      • Coresh J.
      • et al.
      New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race.
      (2021-CKD-EPI) to construct an alternative cohort. Race and ethnicity were self-reported. We defined incident CKD by the first occurrence of two consecutive eGFR <60 mL/min/1.73m2 at ≥91 days apart but within 18 months.

      Levey AS, Coresh J, Balk E, et al. National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med. 2003;139(2):137-147. doi:200307150-00013 [pii]

      Follow-up time started from the second, confirmatory, eGFR value in each cohort to avoid immortal time bias and continued up to 10 years or May 31, 2018. For each cohort, we obtained hazard ratios of death (including death after KRT) for Blacks versus Whites using Cox proportional hazards regression and for KRT using cause-specific hazards regression censored for death. Additional description is provided in Item S1. This study was approved by Institutional Review Boards.
      Between January 2007 and December 2016, 84,090 Black and 507,303 White veterans had incident CKD defined by 2009-CKD-EPI; and 101,693 Black (including 67,038 [66%] who were in both cohorts and 34,655 [34%] patients new to this cohort) and 449,802 White veterans (366,118 [81%] in both cohorts and 83,684 [19%] new patients) had incident CKD by 2021-CKD-EPI. Some patients identified by 2009-CKD-EPI were not identified as incident CKD by 2021-CKD-EPI (Item S2). The Black race group defined by 2021-CKD-EPI was younger and had fewer comorbid conditions compared with its counterpart by 2009-CKD-EPI (Table 1), primarily due to inclusion of younger and healthier Black veterans identified by 2021-CKD-EPI (Table S1). Conversely, the White group by 2021-CKD-EPI was slightly older with more comorbid conditions (Table 1), primarily due to removal of some healthier Whites from its incident CKD group (Table S1). Rates of KRT (10.5 vs. 15.2 per 1000 patient-years) and death (51.6 vs. 62.9 per 1000 patient-years) were both substantially reduced in Black veterans using 2021-CKD-EPI vs. 2009-CKD-EPI (Table 2). Conversely, rates of KRT and death were both increased in White veterans. After adjustment for basic covariates, Black veterans had a 37% greater hazard rate of KRT than White veterans under 2021-CKD-EPI, a marked reduction from the 172% greater Black-vs.-White hazard rate under 2009-CKD-EPI. Also, Black veterans had a 9% lower adjusted hazard rate of death than Whites under 2021-CKD-EPI, in contrast to a 10% greater adjusted hazard of death with 2009-CKD-EPI. These disparities were similar after further adjustment for comorbidities.
      Table 1Baseline characteristics of the Black and White veterans at incidence of CKD defined by the 2021 and 2009 CKD-EPI equations
      CharacteristicIdentified by the 2021 CKD-EPI (n=551,495)Identified by the 2009 CKD-EPI (n=591,393)
      BlackWhiteBlackWhite
      Number of participants101,693449,80284,090507,303
      Age, mean (SD), yrs65.3 (10.2)74.1 (9.6)67.0 (10.3)73.2 (9.6)
      Age <65 years, n (%)52,656 (51.8)80,685 (17.9)37,875 (45.0)103,429 (20.4)
      Age ≥65 years, n (%)49,037 (48.2)369,117 (82.1)46,215 (55.0)403,874 (79.6)
      Male, n (%)96,095 (94.5)437,603 (97.3)80,234 (95.4)492,891 (97.2)
      BMI, mean (SD), kg/m
      • Vyas D.A.
      • Eisenstein L.G.
      • Jones D.S.
      Hidden in Plain Sight - Reconsidering the Use of Race Correction in Clinical Algorithms.
      29.8 (6.3)29.9 (6.0)29.8 (6.5)29.9 (5.9)
      Systolic BP, mean (SD), mm Hg133.0 (19.8)130.2 (18.2)133.4 (20.4)130.3 (17.9)
      Diastolic BP, mean (SD), mm Hg77.1 (12.3)71.2 (11.1)76.3 (12.6)71.8 (11.1)
      eGFR, mean (SD), mL/min per 1.73 m251.2 (8.4)51.4 (7.8)50.6 (8.9)51.4 (7.8)
      Hypertension, n (%)94,644 (93.1)416,629 (92.6)80,320 (95.5)461,841 (91.0)
      Diabetes, n (%)54,467 (53.6)230,136 (51.2)49,053 (58.3)246,490 (48.6)
      Heart failure, n (%)21,653 (21.3)130,674 (29.1)21,235 (25.3)132,569 (26.1)
      Coronary artery disease, n (%)33,652 (33.1)242,851 (54.0)31,835 (37.9)259,190 (51.1)
      Cardiac dysrhythmia, n (%)27,377 (26.9)198,826 (44.2)25,425 (30.2)211,704 (41.7)
      Other cardiac diseases, n (%)29,208 (28.7)185,218 (41.2)26,507 (31.5)198,232 (39.1)
      CVA/TIA, n (%)19,497 (19.2)129,699 (28.8)18,179 (21.6)137,146 (27.0)
      PVD, n (%)24,310 (23.9)164,778 (36.6)22,826 (27.1)174,148 (34.3)
      COPD, n (%)26,390 (26.0)165,477 (36.8)23,168 (27.6)181,023 (35.7)
      Anemia, n (%)38,656 (38.0)179,468 (39.9)36,180 (43.0)185,669 (36.6)
      Cancer, n (%)23,490 (23.1)124,088 (27.6)21,364 (25.4)134,297 (26.5)
      GI, n (%)13,880 (13.6)64,031 (14.2)12,310 (14.6)68,880 (13.6)
      Liver disease, n (%)6581 (6.5)24,696 (5.5)5,656 (6.7)27,478 (5.4)
      UACR, mg/g, n (%)
      <3025,698 (25.3)117,343 (26.1)21,127 (25.1)132,422 (26.1)
      30-30012,596 (12.4)59,265 (13.2)11,946 (14.2)60,357 (11.9)
      >3004,946 (4.9)16,282 (3.6)5,336 (6.3)15,216 (3.0)
      Missing58,453 (57.5)256,912 (57.1)45,681 (54.3)299,308 (59.0)
      Incident years 2007-1033,672 (33.1)172,355 (38.3)27,715 (33.0)197,405 (38.9)
      Incident years 2011-1328,171 (27.7)121,379 (27.0)23,542 (28.0)134,849 (26.6)
      Incident years 2014-1639,850 (39.2)156,068 (34.7)32,833 (39.0)175,049 (34.5)
      Summing multiple categories in the same variable may not be 100% due to rounding.
      Abbreviations: SD, standard deviation; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration equation; BMI, body mass index; BP, blood pressure; eGFR, estimated glomerular filtration rate; CVA/TIA, cerebrovascular accident or transient ischemic attack; PVD, peripheral vascular disease; COPD, chronic obstructive pulmonary disease; GI, gastrointestinal bleeding disorders; UACR, urine albumin-to-creatinine ratio.
      Table 2Hazard ratios of outcomes for Black veterans compared to White veterans with incident CKD defined by each equation
      KRTDeath
      Event rate (per 1000 patient-years)Unadjusted hazard ratio (95% CI)Hazard ratio (95% CI), adjusted for basic covariatesaHazard ratio (95% CI), additionally adjusted for comorbiditiesbEvent rate (per 1000 patient-years)Unadjusted hazard ratio (95% CI)Hazard ratio (95% CI), adjusted for basic covariatesaHazard ratio (95% CI), additionally adjusted for comorbiditiesb
      2021 CKD-EPI c
      Black10.52.39 (2.31-2.47)1.37 (1.32-1.42)1.27 (1.22-1.32)51.60.62 (0.61-0.62)0.91 (0.90-0.92)0.96 (0.94-0.97)
      White4.4ReferenceReferenceReference83.5ReferenceReferenceReference
      2009 CKD-EPI c
      Black15.24.56 (4.40-4.71)2.72 (2.62-2.82)2.21 (2.13-2.29)62.90.85 (0.84-0.86)1.10 (1.09-1.12)1.10 (1.08-1.11)
      White3.4ReferenceReferenceReference74.3ReferenceReferenceReference
      a Basic covariates included age, sex, eGFR and incident-year period.
      b Covariates were basic covariates (age, sex, eGFR and incident-year period), plus body mass index, systolic and diastolic blood pressures, and 13 comorbidities (hypertension, diabetes, heart failure, coronary artery disease, cardiac dysrhythmia, other cardiac diseases, cerebrovascular accident/transient ischemic attack, peripheral vascular disease, chronic obstructive pulmonary disease, anemia, cancer, gastrointestinal bleeding disorders, and liver disease).
      C Analyses were performed separately for the two equations. For each equation, Black veterans were compared to the White veterans.
      Abbreviations: CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration equation; KRT, kidney replacement therapy; CI, confidence interval; eGFR, estimated glomerular filtration rate.
      In this national veteran population, we found that the 2021 CKD-EPI resulted in smaller estimates of racial disparities in clinical outcomes, but a greater disparity in age of CKD onset and many comorbidities at incident CKD. A main strength of the study is that the comparison was robust because all groups of veterans were anchored in new diagnosis of, or incident, CKD according to the equation and were followed for extended duration. The main limitation is the predominance of male participants in VHA.
      These findings have important implications. Despite no change in actual patient outcomes, our disparity estimates of clinical outcomes between non-Hispanic Blacks and Whites following incident CKD changed substantially by the new 2021 CKD-EPI equation because it changes eGFR values for both races, resulting in different incident CKD cohorts of both races. The research community should consider how to interpret prior and future estimates of disparities based on different eGFR equations. Our findings also suggest that the 2021 equation will identify more Black adults with CKD who are younger and relatively healthier. This will provide an important opportunity for health care providers to engage and intervene early to mitigate risks of progression and adverse outcomes in this high-risk group.
      Acknowledgements: Support for VA/CMS data was provided by the Department of Veterans Affairs, VA Health Services Research and Development Service, VA Information Resource Center (Project Numbers SDR 02-237 and 98-004). This work was also supported using resources and facilities at the Veterans Informatics and Computing Infrastructure (VINCI), VA HSR RES 13-457. Accessing VA national databases and computations was supported by the VINCI team in Salt Lake City, Utah.

      Supplementary data

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