Association of Estimated GFR Calculated Using Race-Free Equations With Kidney Failure and Mortality by Black vs Non-Black Race

Abstract

for the Chronic Kidney Disease Prognosis Consortium IMPORTANCE At a given estimated glomerular filtration rate (eGFR), individuals who are Black have higher rates of mortality and kidney failure with replacement therapy (KFRT) compared with those who are non-Black. Whether the recently adopted eGFR equations without race preserve racial differences in risk of mortality and KFRT at a given eGFR is unknown.OBJECTIVE To assess whether eGFR equations with and without race and cystatin C document racial differences in risk of KFRT and mortality in populations including Black and non-Black participants.DESIGN, SETTING, AND PARTICIPANTS Retrospective individual-level data analysis of 62 011 participants from 5 general population and 3 chronic kidney disease (CKD) US-based cohorts with serum creatinine, cystatin C, and follow-up for KFRT and mortality from 1988 to 2018.EXPOSURES Chronic Kidney Disease Epidemiology Collaboration equation with serum creatinine (eGFRcr with and without race), cystatin C (eGFRcys without race), or both markers (eGFRcr-cys without race). MAIN OUTCOMES AND MEASURESThe prevalence of decreased eGFR at baseline and hazard ratios of KFRT and mortality in Black vs non-Black participants were calculated, adjusted for age and sex. Analyses were performed within each cohort and with random-effect meta-analyses of the models. RESULTS Among 62 011 participants (20 773 Black and 41 238 non-Black; mean age, 63 years; 53% women), the prevalence ratio (95% CI; percent prevalences) of eGFR less than 60 mL/min/1.73 m 2 comparing Black with non-Black participants was 0.98 (95% CI, 0.93-1.03; 11% vs 12%) for eGFRcr with race, 0.95 (95% CI, 0.91-0.98; 17% vs 18%) for eGFRcys, and 1.2 (95% CI, 1.2-1.3; 13% vs 11%) for eGFRcr-cys but was 1.8 (95% CI, 1.7-1.8; 15% vs 9%) for eGFRcr without race. During a mean follow-up of 13 years, 8% and 4% of Black and non-Black participants experienced KFRT and 34% and 39% died, respectively. Decreased eGFR was associated with significantly greater risk of both outcomes for all equations. At an eGFR of 60 mL/min/1.73 m 2 , the hazard ratios for KFRT comparing Black with non-Black participants were 2.8 (95% CI, 1.6-4.9) for eGFRcr with race, 3.0 (95% CI, 1.5-5.8) for eGFRcys, and 2.8 (95% CI, 1.4-5.4) for eGFRcr-cys vs 1.3 (95% CI, 0.8-2.1) for eGFRcr without race. The 5-year absolute risk differences for KFRT comparing Black with non-Black participants were 1.4% (95% CI, 0.2%-2.6%) for eGFRcr with race, 1.1% (95% CI, 0.2%-1.9%) for eGFRcys, and 1.3% (95% CI, 0%-2.6%) for eGFRcr-cys vs 0.37% (95% CI, −0.32% to 1.05%) for eGFRcr without race. Similar patterns were observed for mortality. CONCLUSIONS AND RELEVANCEIn this retrospective analysis of 8 US cohorts including Black and non-Black individuals, the eGFR equation without race that included creatinine and cystatin C, but not the eGFR equation without race that included creatinine without cystatin C, demonstrated racial differences in the risk of KFRT and mortality throughout the range of eGFR. The eGFRcr-cys equation may be pr...

Serum Cystatin C for Estimation of GFR

“…5 Use of serum cystatin C is recommended by the 2021 National Kidney Foundation and American Society of Nephrology Task Force to estimate GFR in adults with or at risk for CKD. 3,4 Serum cystatin C is a low-molecular-weight protein found in all tissues in the body. It is filtered at the glomerulus and not secreted into the renal tubules or reabsorbed into the bloodstream.…”

European Kidney Function Consortium Equation vs. Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Refit Equations for Estimating Glomerular Filtration Rate: Comparison with CKD-EPI Equations in the Korean Population

“…Inker LA et al [ 18 ] reported that the CKD-EPI equation overestimated mGFR by a median of 0.5 mL/min/1.73 m 2 and the CKD-EPI-R equation overestimated mGFR by a median of 3.9 mL/min/1.73 m 2 ; the mean difference was −3.4 mL/min/1.73 m 2 in non-Blacks [ 18 ]. Recent studies showed that there is a discrepancy between mGFR and eGFR, even in individual levels [ 40 , 41 ]. Although we could not compare eGFR with mGFR directly, the present study also showed the same mean difference (−3.4 mL/min/1.73 m 2 ) between CKD-EPI and CKD-EPI-R equations ( Table 1 ).…”

Race, ancestry, and genetic risk for kidney failure

“…Gutiérrez et al. 1 recognized that when assessing population-level disease prevalence of CKD, the elimination of the race modifier from the eGFR equation increased the estimated prevalence of CKD in the Black population by 2% and lowered the estimated prevalence of CKD in non-Black population by 1.5% compared with earlier 2009 CKD-EPI eGFR equations that included race. 4 However, whether the race-free formula alters the relation of reduced eGFR values with the rates of KFRT and mortality within and between racial groups was unclear, leading them to undertake this study.…”

“…

In a retrospective analysis of over 62,000 Black and non-Black participants from eight United States cohorts, Gutie ´rrez et al 1 examined estimated glomerular filtration rate (eGFR) equations to assess racial differences in kidney failure requiring replacement therapy and in mortality across different equations.

…”

“…Key limitations in this study included low enrollment of racial and ethnic groups other than Black and non-Hispanic White, potential heterogeneity in the methods of measurement across different cohorts and different time periods, and the lack of information on the many structural drivers of health, which are inequitably distributed across racial groups and may mediate much of the observed race-based associations. The work by Gutie ´rrez et al 1 has identified important differences between various eGFR formulas for assessing racial group risk of KFRT and mortality, which could have important public health implications. Conventional approaches to studying KFRT and mortality have relied uncritically on biological determinism.…”