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GFR Can Be Accurately Estimated Without Race Using New Creatinine- and Cystatin C–Based Equations
TAKE-HOME MESSAGE
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This study used data from two datasets to develop new estimated glomerular filtration rate (eGFR) equations that do not incorporate race and then validated the equations using a dataset of 12 studies. Measured GFR was overestimated in Blacks and, to a lesser extent, in other patients when the current creatinine equation was applied to data from the validation dataset. Removing race from the equation led to underestimation of measured GFR in Blacks. Measured GFR was underestimated in Blacks and overestimated in non-Blacks by a new equation using age and sex without race. Compared with new equations that incorporate creatinine alone, new equations that incorporate creatinine and cystatin C were more accurate and reduced the difference by race. Compared with the other new equations, the new creatinine–cystatin C equations had less effect on population estimates of chronic kidney disease (CKD).
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Although new creatinine equations presented in this paper may be sufficiently accurate for routine clinical practice, new equations incorporating creatinine and cystatin C appear to be preferable when possible as they produce more accurate results with smaller differences by race. However, there is a need to determine whether these findings are consistent in acute care settings.
abstract
This abstract is available on the publisher's site.
Access this abstract nowBACKGROUND
Current equations for estimated glomerular filtration rate (eGFR) that use serum creatinine or cystatin C incorporate age, sex, and race to estimate measured GFR. However, race in eGFR equations is a social and not a biologic construct.
METHODS
We developed new eGFR equations without race using data from two development data sets: 10 studies (8254 participants, 31.5% Black) for serum creatinine and 13 studies (5352 participants, 39.7% Black) for both serum creatinine and cystatin C. In a validation data set of 12 studies (4050 participants, 14.3% Black), we compared the accuracy of new eGFR equations to measured GFR. We projected the prevalence of chronic kidney disease (CKD) and GFR stages in a sample of U.S. adults, using current and new equations.
RESULTS
In the validation data set, the current creatinine equation that uses age, sex, and race overestimated measured GFR in Blacks (median, 3.7 ml per minute per 1.73 m2 of body-surface area; 95% confidence interval [CI], 1.8 to 5.4) and to a lesser degree in non-Blacks (median, 0.5 ml per minute per 1.73 m2; 95% CI, 0.0 to 0.9). When the adjustment for Black race was omitted from the current eGFR equation, measured GFR in Blacks was underestimated (median, 7.1 ml per minute per 1.73 m2; 95% CI, 5.9 to 8.8). A new equation using age and sex and omitting race underestimated measured GFR in Blacks (median, 3.6 ml per minute per 1.73 m2; 95% CI, 1.8 to 5.5) and overestimated measured GFR in non-Blacks (median, 3.9 ml per minute per 1.73 m2; 95% CI, 3.4 to 4.4). For all equations, 85% or more of the eGFRs for Blacks and non-Blacks were within 30% of measured GFR. New creatinine-cystatin C equations without race were more accurate than new creatinine equations, with smaller differences between race groups. As compared with the current creatinine equation, the new creatinine equations, but not the new creatinine-cystatin C equations, increased population estimates of CKD prevalence among Blacks and yielded similar or lower prevalence among non-Blacks.
CONCLUSIONS
New eGFR equations that incorporate creatinine and cystatin C but omit race are more accurate and led to smaller differences between Black participants and non-Black participants than new equations without race with either creatinine or cystatin C alone. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases.)
Additional Info
Disclosure statements are available on the authors' profiles:
New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race
N. Engl. J. Med 2021 Sep 23;[EPub Ahead of Print], LA Inker, ND Eneanya, J Coresh, H Tighiouart, D Wang, Y Sang, DC Crews, A Doria, MM Estrella, M Froissart, ME Grams, T Greene, A Grubb, V Gudnason, OM Gutiérrez, R Kalil, AB Karger, M Mauer, G Navis, RG Nelson, ED Poggio, R Rodby, P Rossing, AD Rule, E Selvin, JC Seegmiller, MG Shlipak, VE Torres, W Yang, SH Ballew, SJ Couture, NR Powe, AS LeveyFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
A national movement to challenge structural racism in medicine is gaining momentum. One form of structural racism in medicine, which is the use of race-based medicine, has been gaining publicity recently thanks to ongoing advocacy to eliminate its flawed use, as well as new research to substantiate these efforts. Perhaps the most prominent example, race-based estimated glomerular filtration rate (eGFR), has gained national attention and scrutiny in recent years.
As race is a sociopolitical construct with no biological nor genetic basis, race should not be used as a proxy for biology, as it is currently erroneously used in many clinical algorithms including race-based eGFR and spirometry. Unlike genetic ancestry and geographic origin, which do have a genetic basis; racial categories on the other hand, were arbitrarily created centuries ago with very specific political intentions, mostly rooted in Eurocentric ideology as justification for colonization, genocide and enslavement of racialized people. This is the historically traumatic reality that we must acknowledge when we practice aspects of medicine steeped in flawed ideologies of racial essentialism. We therefore have a responsibility to interrupt the perpetuation of racism in our medical practice that is systematically harming patients. The role of racism is ultimately the risk factor that should be scrutinized when examining the root causes of inequitable health outcomes, not race.
For estimating GFR in current practice, characteristics including age, sex, and race are taken into account to estimate GFR, and results are reported in a binary, with one result for non-Black patients and another result for Black patients (with a race correction coefficient applied to the latter). This race-corrected binary reporting has been shown to systematically lead to and exacerbate racial health disparities; a recent study found that the removal of the race correction factor and subsequent re-staging of chronic kidney disease would make 14,000 Black patients newly eligible for kidney transplants, and 60,000 newly eligible for specialist referral.
In attempt to mitigate these harms, this NEJM article, “New Creatinine- and Cystatin C–Based Equations to Estimate GFR without Race,” outlines a path away from the use of race as a flawed proxy for biology in clinical algorithms. This study developed new race-free eGFR equations utilizing the data sets previously used for development of current existing (race-based) equations. The authors analyzed the new eGFR equations that take into account creatinine and cystatin C without race and concluded that they are more accurate than older equations that include race. This is an encouraging step in the right direction as far as seeing more efforts in research going towards the creation and examination of more accurate clinical algorithms that do not continue to conflate race with biology and propagate systematic racial bias.
This research is welcomed as advocates for antiracism in medicine have called for swift policy changes over the last several years leading up to this study, including successful efforts to eliminate race-based eGFR reporting at such medical institutions as San Francisco General Hospital, University of California San Francisco, University of Washington, Vanderbilt University Medical Center, Mass General Brigham, and numerous others, thanks to the leadership of many health justice advocates including the organizing efforts centralized at Institute for Healing and Justice in Medicine.
It is encouraging to see the progress that has been made in challenging structural racism in medicine over the past few years. Several major professional organizations such as American Academy of Family Physicians as well as the American Medical Association, have passed policy resolutions officially taking a stance to reject flawed notions of race-based medicine. And now, thanks to the aforementioned advocacy and studies like this one, the National Kidney Foundation and American Society for Nephrology now recommend the use of the new, race-free 2021 CKD-EPI Creatinine Equation to estimate GFR as of September 2021.