eGFR from serum creatinine–based equations informs diagnosis and staging of CKD. The guideline-recommended Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-based equation includes age, sex, and race (Black versus non-Black) variables and increases the eGFR estimate by approximately 16% for Black compared with non-Black persons of the same age and sex. The consideration of Black race in eGFR calculations has led to concerns that this may lead to systematically different care and harm to Black persons; however, removal of the race coefficient from eGFR equations may increase error in GFR estimation among Black individuals, thereby decreasing the validity of eGFR as a biomarker (1).
CKD is diagnosed and jointly staged by eGFR and albuminuria, which independently associate with adverse outcomes. In addition to prognostic importance, CKD staging by eGFR has demonstrated validity through higher prevalence of CKD-related complications with more severe CKD stage, including anemia, acidosis, hyperphosphatemia, and hypertension (2). How the prevalences of CKD complications change with removal of the Black race coefficient is unknown. We estimated the prevalences of four common CKD complications and related medication use among Black persons in the United States by CKD G stage categorized from eGFR calculated without versus with the race coefficient and compared with the non-Black population.
We used data from the US National Health and Nutrition Examination Survey (NHANES), a population-based study of individuals that uses probability sampling to allow estimates for the noninstitutionalized, civilian population. NHANES was approved by the National Center for Health Statistics Institutional Review Board, and participants gave informed consent. We combined four 2-year cycles (2011–2018) and adjusted the weights accordingly, enabling stable estimates of cross-sectional population totals and proportions. We used survey methods for all analyses, to account for clustering, stratification, and weighting, and Taylor series linearization for variance estimation. We included individuals ≥20 years old who took part in the NHANES exam, classified by self-reported race into Black and non-Black groups. GFR was estimated using CKD-EPI, and CKD was staged per Kidney Disease Improving Global Outcomes (KDIGO) guidelines. We classified anemia per the World Health Organization definition (hemoglobin <12 g/dl in females, <13 g/dl in males), acidosis as serum bicarbonate ≤22 mEq/L, hyperphosphatemia at ≥4.5 mg/dl, and stage 2 hypertension as systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg. Iron supplementation was inferred from prescription iron use or dietary supplementation ≥25 mg/day. Phosphate binder use was inferred from prescription binder use or calcium supplementation ≥600 mg/day.
There were an estimated 29,225,067 (95% confidence interval [95% CI], 27,584,126 to 30,866,009) persons in the United States with eGFR<60 ml/min per 1.73 m2 without the race coefficient. Of these, an estimated 19.0% (95% CI, 16.0% to 22.4%) were Black, and 81% (95% CI, 77.6% to 84.0%) were non-Black. Of Black persons with eGFR<60 ml/min per 1.73 m2 without the race coefficient, 85.4% (95% CI, 82.7% to 87.7%) had at least one of the four CKD complications; using eGFR with the race coefficient, 91.8% (95% CI, 89.1% to 93.8%) had at least one complication. Of non-Black persons with eGFR<60 ml/min per 1.73 m2, 74.8% (95% CI, 71.8% to 77.6%) had at least one complication. Figure 1 presents results for the four CKD complications by CKD G-stage and race, without versus with the race coefficient in the eGFR estimating equation. With removal of the race coefficient, estimated prevalences of the four complications decreased only slightly in some CKD strata of Black persons, most pronouncedly for anemia in earlier stage CKD. Qualitative comparisons of the prevalence of complications between Black persons and non-Black persons of the same CKD G-stage were largely unchanged by removal of the race coefficient; in particular, no complications decreased in prevalence to below the levels seen in the non-Black group. No substantive changes in corresponding medication uses were identified either.
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Figure 1.: CKD-related complication prevalences and medication use. Estimated proportions of CKD subgroups with CKD-related complications (A) and medication usage (B). The points represent estimated proportions, and the lines represent 95% confidence intervals for the estimates. CKD subgroups are defined by G-stage and by three race/eGFR estimating equation categories: Black race, eGFR estimated with race coefficient; Black race, eGFR estimated without race coefficient; and non-Black race. KDIGO CKD G classifications based on eGFR are used (G1/G2: ≥60 ml/min per 1.73 m2; G3a: 45–59; G3b: 30–44; G4: 15–29; G5<15). eGFR was estimated using the CKD-EPI creatinine equation, without and with the race coefficient, and thus eGFR estimates changed only for Black persons. Calcium supplementation (defined as daily elemental calcium in supplements ≥600 mg) extracted as over the counter calcium carbonate has been used as a phosphate binder in some circumstances. coef., coefficient; KDIGO, Kidney Disease Improving Global Outcomes; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration.
Although our analysis found that the relationship of CKD G-stage with certain comorbidities changed little, in other areas, substantial effects of removing the Black race coefficient have been identified. Investigators have estimated that nearly 1 million additional Black persons in the United States would be classified with CKD (3). There is substantial potential impact on kidney donation and medication eligibility, with an estimated 1.2% of Black adults having eGFR change potentially affecting eligibility for common medication classes (4). Another analysis found that removing the Black race coefficient could reduce kidney transplant disparities (5).
Our study has limitations. The analysis used weights that were not derived for the subpopulation. CKD G-stage was estimated using single creatinine measurements, and complications were estimated using single measurements, except for blood pressures, which were the average of up to four measurements from a single exam. This study does not address accuracy of eGFR nor many important hindrances to fair, equitable kidney care outlined in recent articles (1).
We found that eGFR estimated without the race coefficient (compared to with the race coefficient) among Black persons in the United States had little effect on the prevalences of four common CKD complications by CKD G-stage. This may allay concerns that changing the eGFR estimation may weaken the meaningfulness of CKD stages among Black persons in the United States.
Disclosures
S.D. Navaneethan is supported by Department of Veterans Affairs Health Services Research & Development grant 1I01HX002917-01A1 AQ9 and National Institutes of Health grant NIDDK-R01DK101500; reports consultancy agreements with and honoraria from Bayer, Boehringer Ingelheim, Tricida, and Vifor; personal fees from REATA; and grants from Keryx, outside the submitted work. S.D. Navaneethan reports employment with the US Department of Veterans Affairs and serves as a scientific advisor or member of American Journal of Kidney Diseases, CJASN, CardioRenal Medicine, Current Opinion in Nephrology and Hypertension, and American Journal of Nephrology and as a Kidney Disease Improving Global Outcomes Guideline writing committee member. W.C. Winkelmayer reports consultancy agreements with and honoraria from Akebia, AstraZeneca, Bayer, Otsuka, and Reata and personal fees from Janssen, Merck, and Vifor FMC Renal Pharma (including Relypsa), outside the submitted work. W.C. Winkelmayer serves as co-chair of Kidney Disease Improving Global Outcomes, an Associate Editor of the Journal of the American Medical Association and is on the Editorial Boards of the American Journal of Kidney Diseases, American Journal of Nephrology, CJASN, and Seminars in Dialysis. The remaining author has nothing to disclose.
Funding
C.P. Walther is supported by National Institute of Diabetes and Digestive and Kidney Diseases grant K23DK122131.
Acknowledgments
The interpretation and reporting of these data are the responsibility of the authors and in no way should be viewed as official policy or interpretation of the Department of Veterans Affairs or the US government. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or Veterans Administration.
References
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2. Inker LA, Coresh J, Levey AS, Tonelli M, Muntner P: Estimated GFR, albuminuria, and complications of chronic kidney disease. J Am Soc Nephrol 22: 2322–2331, 2011
3. Bragg-Gresham J, Zhang X, Le D, Heung M, Shahinian V, Morgenstern H, et al.: Prevalence of chronic kidney disease among black individuals in the US after removal of the black race coefficient from a glomerular filtration rate estimating equation. JAMA Netw Open 4: e2035636, 2021
4. Diao JA, Wu GJ, Taylor HA, Tucker JK, Powe NR, Kohane IS, et al.: Clinical implications of removing race from estimates of kidney function. JAMA 325: 184–186, 2021
5. Zelnick LR, Leca N, Young B, Bansal N: Association of the estimated glomerular filtration rate with vs without a coefficient for race with time to eligibility for kidney transplant. JAMA Netw Open 4: e2034004, 2021
