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Kidney Disease, Race, and GFR Estimation.

ABSTRACT: Assessment of GFR is central to clinical practice, research, and public health. Current Kidney Disease Improving Global Outcomes guidelines recommend measurement of serum creatinine to estimate GFR as the initial step in GFR evaluation. Serum creatinine is influenced by creatinine metabolism as well as GFR; hence, all equations to estimate GFR from serum creatinine include surrogates for muscle mass, such as age, sex, race, height, or weight. The guideline-recommended equation in adults (the 2009 Chronic Kidney Disease Epidemiology Collaboration creatinine equation) includes a term for race (specified as black versus nonblack), which improves the accuracy of GFR estimation by accounting for differences in non-GFR determinants of serum creatinine by race in the study populations used to develop the equation. In that study, blacks had a 16% higher average measured GFR compared with nonblacks with the same age, sex, and serum creatinine. The reasons for this difference are only partly understood, and the use of race in GFR estimation has limitations. Some have proposed eliminating the race coefficient, but this would induce a systematic underestimation of measured GFR in blacks, with potential unintended consequences at the individual and population levels. We propose a more cautious approach that maintains and improves accuracy of GFR estimates and avoids disadvantaging any racial group. We suggest full disclosure of use of race in GFR estimation, accommodation of those who decline to identify their race, and shared decision making between health care providers and patients. We also suggest mindful use of cystatin C as a confirmatory test as well as clearance measurements. It would be preferable to avoid specification of race in GFR estimation if there was a superior, evidence-based substitute. The goal of future research should be to develop more accurate methods for GFR estimation that do not require use of race or other demographic characteristics.

SUBMITTER: Levey AS

PROVIDER: S-EPMC7409747 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceAt 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.ObjectiveTo 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 participantsRetrospective 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.ExposuresChronic 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.ResultsAmong 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 m2 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 m2, 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 preferable to the eGFRcr equation without race for assessing racial differences in the risk of KFRT and mortality associated with low eGFR.

Project description:Rationale & objectiveRecent reassessment of the use of race in estimated glomerular filtration rate (eGFR) in adults has instigated questions about the role of race in eGFR expressions for children. Little research has examined the associations of self-reported race with measured GFR (mGFR) adjusting for serum creatinine or cystatin C in children and young adults with chronic kidney disease (CKD). This study examined these associations and evaluated the performance of the previously published "U25" (under the age of 25 years) eGFR equations in a large cohort of children and young adults with CKD.Study designObservational cohort study.Setting & participantsParticipants in the Chronic Kidney Disease in Children (CKiD) study including 190 Black and 675 non-Black participants contributing 473 and 1,897 annual person-visits, respectively.ExposureSelf- or parental-reported race (Black, non-Black). Adjustment for serum creatinine or cystatin C, body size, and socioeconomic status.OutcomemGFR based on iohexol clearance.Analytical approachLinear regression with generalized estimating equations, stratified by age (<6, 6-12, 12-18, and ≥18 years) incorporating serum creatinine or serum cystatin C. Contrasting performance in different self-reported racial groups of the U25 eGFR equations.ResultsSelf-reported Black race was significantly associated with 12.8% higher mGFR among children in regression models including serum creatinine. Self-reported Black race was significantly associated with 3.5% lower mGFR after adjustment for cystatin C overall but was not significant for those over 12 years. The results were similar after adjustment for body size and socioeconomic factors. The average of creatinine- and cystatin C-based U25 equations was unbiased by self-reported race groups.LimitationsSmall number of children < 6 years; lean body mass was estimated.ConclusionsDifferences in the creatinine-mGFR relationship by self-reported race were observed in children and young adults with CKD and were consistent with findings in adults. Smaller and opposite differences were observed for the cystatin C-mGFR relationship, especially in the younger age group. We recommend inclusion of children for future investigations of biomarkers to estimate GFR. Importantly, for GFR estimation among those under 25 years of age, the average of the new U25 creatinine and cystatin C equations without race coefficients yields unbiased estimates of mGFR.

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Kidney Disease, Race, and GFR Estimation.

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