Race-neutral measures as an equitable path forward

The article entitled “Performance of race-neutral estimated Glomerular FIltration Rate (eGFR) equations in patients with decompensated cirrhosis” by Fallahzadeh et al1 raises two fundamental issues of importance in transplantation. The first issue is the elimination of race as a component in our clinical measures. The second key issue raised is the need to ensure the accuracy of our current race-neutral measures and the need to develop better measures to ensure equity in health care. RACE-BASED MEASURES IN MEDICINE Race is not a surrogate for any underlying definitive biological difference. Evolutionary biologists have shown that socially constructed racial categories such as Black or White do not correlate with genetic variation.2 In 2003, the human genome project showed that humans are 99.9% identical genetically, there is no genetic basis for race, and there was more genetic variation within racial categories in many populations than between them.3 Social scientists recognize race as a social construct that categorizes individuals according to phenotypes, originally devised for the purpose of assigning value in a social hierarchy.2 This original deviant etiology and use of race has permeated the practice of medicine for centuries and has led to significant health inequities. The article by Fallahzadeh and colleagues highlights the important step of moving away from race-based measures in Glomerular Filtration Rate (GFR). This key first step is an important development in our ability to provide equitable care and access to transplantation. Prior race-based GFR measurements were flawed because of their reliance on underpowered analyses with limited data that are further biased by anecdotal assumptions around race-related diet and muscle mass despite no objective data. The use of these biased measures contributed directly to inequitable access to transplantation. An analysis of these flawed race-based GFR measures showed that removing the race coefficient would reclassify 3.1% of Black patients from eGFR >20 mL/min/1.73 m2 to eGFR ≤20 mL/min/1.73 m2, making them eligible for a transplant referral.4 Hence the use of prior race-based GFR equations disadvantaged Black patients when it came to access to transplantation. The elimination of race-based measures is an equity issue and an important step toward addressing disparities in multiple areas of medicine, including in transplantation. That being said, simply no longer using these types of measures is not enough. We must ensure new measures are adequate and develop new measures if needed. DEVELOPMENT OF RACE-NEUTRAL MEASURES IN MEDICINE In recognizing the need to utilize measures that are not race based, there has appropriately been a shift in the measurement of GFR. The assessment of kidney function is further complicated by comorbidities such as end-stage liver disease and cirrhosis. This important analysis by Fallahzadeh and colleagues highlights the differences in accuracy among various measures of kidney function that are race-neutral. They found that the race-neutral eGFR equation CKD-EPI 2021 had low bias across the entire range of GFR and has accuracy as good or better than other equations, but it may not measure kidney function as accurately in cirrhosis, specifically at low GFR, and it underestimated eGFR in Blacks. As we move toward equity in medicine, it is important to assess the validity of our tools and measures across relevant categories of patient populations we manage. The differences across race-neutral measures of kidney function in this analysis as it pertains to race and GFR level highlight the importance of this. Without these types of analyses, we may adopt race-neutral measures that are just as biased and inaccurate as the race-based measures they were created to replace. However, in the setting of identifying gaps in our ability to accurately measure GFR or other key health measures, we must prioritize the development of new and accurate race-neutral measures. In this analysis, Fallahzadeh and colleagues focus on kidney function, but similar conversations should be had pertaining to other areas of medicine, including pulmonary disease and cardiovascular disease. Clinical algorithms based on race have been adopted across medicine, and many have not been validated, yet they still inform treatment.5 We must commit to defining new race-neutral measures in medicine. The development of such measures must include analyses powered to accurately represent potential racial, ethnic, and gender-based differences to ensure the validity of such measures and algorithms across the relevant patient populations we treat. RACE AND GENETICS IN MEDICINE While we recognize the issue of race as a social construct, we must clarify that genetic differences can inform management decisions and outcomes in medicine and should be considered when developing algorithms for treatment. For many years, disparate outcomes in response to interferon-based therapies for hepatitis C based on race were observed. However, these disparities were not because patients were Black, but were largely due to differing distributions of IL28B polymorphisms based on race, and the impact of IL28B genotype on clearance of virus and response to treatment with ribavirin/interferon. Outcomes were worse among all individuals, regardless of race, who had the lower responding polymorphism. Thus, outcomes were worse among Black patients due to overall higher rates of 1 IL28B polymorphism—not because they were Black.6 Fortunately, this is no longer the case in the direct-acting antiviral era of treatment for hepatitis C7 but highlights a clinical scenario where a genetic polymorphism, found among all races and ethnicities, but more predominant in some, resulted in racial differences with respect to outcomes.6 The key issue here is that the polymorphism drove the differences in outcomes, not the race of the patient. This distinct but subtle difference is a key factor in properly contextualizing the use of race and genetics as a means of informing patient care. RACE-NEUTRAL MEASURES AS AN EQUITABLE PATH FORWARD The article by Fallahzadeh and colleagues is an example of the type of research we must prioritize as we move away from race-based clinical measures. We must confirm the accuracy of our new race-neutral measures. In the setting of developing new measures, we must develop these in systematic ways to ensure they are representative of the patient populations we treat and that they accurately reflect the outcomes of interest. This movement toward race-neutral measures has been a long time coming. No doubt, we have perpetuated disparate outcomes in terms of both morbidity and mortality due to our reliance on race-based measures in the past. But, we are now moving toward more equitable care in medicine, focusing on measures that allow us to provide the highest quality equitable care to all of our patients. As we take these important steps forward, we will continue to identify genetic variations that will help inform treatment options for the diverse patient populations we treat. However, these processes will be built on the firm foundation of genetic variation and not solely on biased anecdotal evidence based on race. The article by Fallahzadeh and colleagues provides important context on how best to move forward with impactful and accurate race-neutral measures to inform equitable care in medicine.