Instalab ResearchThe idea of adjusting eGFR for African American patients stems from clinical studies conducted in the late 20th century, particularly the development of the Modification of Diet in Renal Disease (MDRD) and later the CKD-EPI equations. Researchers observed that, on average, African American participants had higher serum creatinine levels than White participants, even when kidney function appeared similar.
Since eGFR is calculated from serum creatinine along with age and sex, this meant that without adjustment, the equations risked underestimating kidney function in African American patients. To correct this, a race coefficient was added, raising the eGFR value for those who identified as African American.
One of the primary reasons cited for the adjustment was the assumption that African Americans, on average, have higher muscle mass compared to other groups. Because creatinine is a byproduct of muscle metabolism, higher muscle mass results in higher baseline serum creatinine levels.
This meant that, without an adjustment, African American patients could be misclassified as having worse kidney function than they truly did. Early validation studies showed that including a race coefficient improved the accuracy of eGFR estimates when compared with measured GFR, particularly in African American study participants.
While early reasoning centered on muscle mass, later research has shown that genetic factors also contribute to differences in kidney health outcomes. Variants in the APOL1 gene, which are more common in individuals of African ancestry, are strongly associated with increased risk of chronic kidney disease and progression to kidney failure. Importantly, these genetic differences influence disease risk but are not directly related to creatinine levels or baseline eGFR.
Although the adjustment was originally added to improve accuracy, over time it became clear that the use of race in eGFR equations was problematic. First, race is a social construct, not a biological category, and self-reported race often does not align neatly with genetic ancestry. For example, two individuals identifying as African American may have very different proportions of African, European, or other ancestry. This variability means that using race as a proxy for biology can be misleading.
Second, studies outside the United States demonstrated that applying the African American adjustment to people of African ancestry in other regions, such as the United Kingdom, led to overestimation of kidney function and under-recognition of chronic kidney disease. This suggests that the adjustment was context-specific and not universally applicable.
Third, the clinical consequences of the adjustment raised serious concerns. By artificially inflating eGFR values in African American patients, the adjustment often delayed diagnosis of kidney disease, referral to nephrology, and eligibility for transplant evaluation. Analyses of national health data showed that removing the adjustment would have resulted in millions more African Americans being classified as having chronic kidney disease, thereby expanding access to specialized care and transplant waitlists.
In recent years, mounting evidence and ethical concerns prompted calls to eliminate race adjustments from clinical algorithms. The National Kidney Foundation and the American Society of Nephrology convened a task force that ultimately recommended replacing race-based eGFR equations with new versions that do not include race.
The CKD-EPI 2021 equation, for example, removes the race variable and instead incorporates both creatinine and cystatin C, another biomarker of kidney function. This approach has been shown to improve accuracy across populations while avoiding the problematic reliance on race.
While the debate over the eGFR race adjustment focuses on clinical equations, it also highlights broader issues of health disparities. African Americans experience disproportionately high rates of chronic kidney disease and kidney failure, driven not just by biology but also by social determinants of health.
Factors such as lower access to healthcare, socioeconomic inequities, higher rates of hypertension and diabetes, and environmental stressors all play major roles in kidney health outcomes. Removing the race adjustment does not by itself solve these inequities, but it is an important step in ensuring that clinical care does not perpetuate structural disparities.
