National and international studies show racialized disparities in chronic kidney disease (CKD) and end-stage renal disease (ESRD), the terminal stage of CKD.[1] CKD has been named an important contributor to both national and global morbidity and mortality, with a vastly disproportionate burden falling on people of color. In America, as of 2013, although the rates of CKD were relatively comparable, Black people had four times the rate of progression to ESRD than non-Hispanic white people.[2] The reasons behind this are complex, with structural factors at the forefront—lack of access to care, environmental toxins, chronic stress, and poverty—all highlighted by Nicholas et al.[3]

Biologically, kidney disease is intimately related to heart disease. Hypertension, or high blood pressure, is a leading cause of CKD, and Black people in the United States have a seventeenfold higher rate of hypertension as the etiology or cause of their ESRD than other populations.[4] [5] An underdiagnoses of hypertension in Black people due to the previously mentioned clinical racism may thus also contribute to disparities in kidney disease, putting Black people at risk for long-term, severe kidney damage. But there are other, more direct issues.

Biological racism is embedded in a key tool used to measure kidney function—the glomerular filtration rate, or GFR. The GFR is a calculated measurement of a particular protein in the blood that the kidneys filter, which is then used to estimate kidney function because kidney function can’t be measured directly in a typical clinic. It provides clinicians with an approximation of how well the kidneys are performing their critical roles of filtering fluid in the body. The GFR is used to diagnose many kidney-related diseases, including CKD. It is thus especially important for classifying severity of CKD (up to and including ESRD) and for making decisions about diagnosis, prognosis, and treatment of kidney disease. Embedding biological race in this tool leads directly to a deadly underdiagnoses of severe kidney disease in Black people, contributing to the disparate epidemic of ESRD and CKD seen today.

The GFR is currently estimated through complex equations that take into account individual factors, including weight, age, sex, serum levels of creatinine (a waste product from muscle breakdown that is excreted in urine), and race. Based on these equations, the further someone’s GFR is below “normal,” the increased severity or stage of kidney disease. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) is the most commonly used equation and was developed in 2009 as an improvement to the 1999 Modification in Diet for Renal Disease (MDRD) study equation.

These two commonly used equations—CKD-EPI and MDRD—each contain a racial adjustment factor coefficient that is multiplied to the baseline GFR estimate for a Black person (1.16 for CKD-EPI; 1.21 for MDRD).[6] This adjustment increases the GFR for a Black person for a given creatinine level in both equations, which means the adjusted GFR is closer to normal and thus creates a diagnosis of a lower disease severity. Compared to a white man of the same age, weight, and serum creatinine level, the estimated GFR of a Black man would be higher, suggesting that Black people have “better kidney function” than individuals of other races. Because of this, Black people must meet higher GFR thresholds of kidney function in order to be diagnosed with kidney disease compared to individuals of other racial groups.

This racial adjustment factor has severe negative clinical implications. Those who identify as (or are identified by their providers as) Black may not be diagnosed early enough, may not receive intervention at a critical period, and are more likely to progress to higher stages of kidney disease and poor health outcomes.[8] The racial adjustment means it takes worse kidney function to get diagnosed with CKD for Black people, and by the time they are diagnosed, they are often at ESRD (CKD is classified as stages 1–5, with ESRD being stage 5). Studies show a two- to fourfold higher incidence (counts of new cases) of ESRD among Black patients as compared with white patients.[9] Yet the prevalence (new cases plus existing cases) of earlier stages of CKD in Black patients is similar or lower than that of white patients, meaning the GFR adjustments may be delaying diagnosis of earlier-stage CKD until Black patients have reached a significantly higher disease burden and are already at ESRD.

Other biological markers beyond GFR help the classification of CKD stages and ESRD, so we would expect those markers to match across CKD staging for different populations if the GFR measurement were accurate. However, white populations with stage 3 CKD display a strikingly lower prevalence of other risk factors for CKD, such as albuminuria and hypertension, compared to the Black populations.[10] This evidence suggests that either white patients are being diagnosed with more severe disease than they actually have or that Black patients are being diagnosed with less severe disease than they actually have. Given the current race coefficients in measuring GFR, this evidence suggests that clinicians may systematically misclassify disease status among Black people to a falsely lower CKD stage (Peralta 2010). Despite having known risk factors for CKD, such as albuminuria and hypertension, young Black people may only be diagnosed once they reach advanced stages of disease.

This all adds up to a disproportionate disease burden. Black patients represent 30 percent of all ESRD patients in the United States, and just 13 percent of the total US population.[11] The only cure for ESRD is a kidney transplant, yet Black patients are less likely to be identified as transplant candidates, more likely to be on waiting lists for longer, and less likely to receive a deceased or living kidney donation compared to white patients due to both institutional and structural factors.[12] Not only is the current race-based system of determining GFR scientifically flawed, but it actively harms Black patients by systematically missing early diagnoses of CKD.

These dire health implications beg the question, Why do racial adjustment factors exist for GFR at all? The National Kidney Foundation states that race is included in CKD-EPI and MDRD equations because “African Americans have a higher GFR than Caucasians at the same level of serum creatinine.”[13] However, this argument is somewhat circular and has many scientific limitations.

The MDRD and CKD-EPI equations appeared in 1999 and 2009, respectively, to improve upon an older equation (Cockcroft-Gault formula) developed in 1973 with a cohort of 249 men. The 1999 MDRD equation was then reformulated in 2005 (right at the time that the research in salt sensitivity was spiking), and the CKD-EPI was created shortly after that. Each equation represents an academic “doubling down” on race in the name of improving the accuracy of estimating kidney function.

First, the demographic profile of each study was crucial to the specific equation development, and often not representative of the United States (e.g., there are generally fewer people of color in the study as a percentage than the percentage of the US population—the MDRD study was 88 percent white). Therefore, extrapolations about the creatinine clearance for more diverse populations along any of the parameters used in the equation are bound to be of limited use.[14] For example, age is a key factor in the equations, and the dataset for MDRD only included older people (average age 50.6) with CKD, which, therefore, may not apply to healthy populations, particularly younger populations. One study showed this was particularly true for young Black people, who may be significantly misclassified with lower or no CKD.[15] And because the formulas were derived from American, mostly white populations, their utility may be limited for multiethnic populations especially in other geographies. A study of multiethnic Brazilian populations showed CKD-EPI has similar accuracy to MDRD regardless of race corrections when compared to the gold-standard direct measurement of GFR function, iohexol clearance.[16]

Second, creators of both the CKD-EPI and MDRD equations do not provide sound evidence for why race was included in the model for calculating GFR in the first place. The authors of the MDRD equation did not include an explanation in their methods for why they included race in their model. In their conclusions, they simply state, “on average, black persons have greater muscle mass than white persons.”[17] The evidence base for this assumption is fundamentally flawed. The three studies the MDRD researchers cited to support their claim were fraught with questionable scientific methods regarding race, including “visual determination” of study participants’ race categorization and grossly racist “anthropometric measures” such as “densitometry” to generalize questions of overall muscle mass across races (Levey et al. 1999; Cohn et al. 1977; Harsha et al. 1978; Worrall et al. 1990).[18] Harsha’s densitometry results are unlikely to hold up today, as he posited that Black children on the whole had much less body fat, while today children of color are far more likely to be obese. This points to the racist assumption that these characteristics were biological instead of structural or societally influenced. The creators of CKD-EPI, which was meant to improve upon MDRD, included race simply based on the fact that MDRD did.[19]

Furthermore, the race categories represented in the equations are arbitrary and do not reflect the heterogeneity of human populations. They reflect the social categories that society has designed, based on arbitrary visual and social standards. The MDRD study never explains how it classified participants by race nor how it defined race, while the CKD-EPI only notes their source data was the National Health and Nutrition Examination Survey, which tends to use self-identification within the given options. These options are typically drawn from the census options, which are both socially constructed and confusing by conflating race with ethnicity. As an example of the limitations of these arbitrary definitions of race, Zanocco’s study of a multiethnic Brazilian population showed that the race adjustment was not associated with better performance in evaluating GFR, demonstrating that it is not a necessary or useful tool in multiethnic populations.[20] Further highlighting the arbitrariness of the racial categories used in calculating GFR, nephrologists have anecdotally admitted to misidentifying patients as African American based on their brown skin, meaning their understanding of the usefulness of the GFR equation is based on visual assumptions.[21] This questions the scientific usefulness of such GFR estimations and highlights the racism inherent at every level of the interaction, from the structural construction of the flawed GFR equation to the interpersonal racism of misidentifying patients based only on skin color.

Third, the equations take into account several biological factors such as age and gender alongside (nonbiological) race, but do not include muscle mass. Muscle mass is crucial in the GFR calculation because creatinine, one of the main serum markers, is a by-product of muscle breakdown. Thus, those with higher muscle mass and those with poor kidney function would both have elevated serum creatinine levels, leading to lower estimated GFRs. The National Kidney Foundation guidelines themselves explain that the estimated GFR calculations are less accurate for patients who do not have an average muscle mass and standard diet, including athletes, people over seventy years old, the malnourished, the obese, vegetarians, or patients with changing kidney function.[22] Although the biological mechanisms by which these factors affect muscle mass are well understood, only age is “adjusted” for in calculating GFR.

However, the variable of race is adjusted for, not muscle mass, and often anecdotally referred to as a proxy for muscle mass without any explanation for why race would be related to muscle mass. A quick Google search will turn up hundreds of papers seeking to justify or explain differences in body habitus (e.g., muscle mass, body mass index, adiposity) with biological mechanisms that are then explicitly or implicitly tied to a biologized notion of race. These papers either ignore social and structural determinants of health (e.g., ignoring the effect that lived experience and environment may have on body composition) or have a blatantly racialized research agenda seeking to uphold a preconceived notion that racialized biological differences exist.[23] Although differences in bodies do exist across different people, the differences are far more nuanced than the social category of race. These notions underscore the existing racist perceptions and stereotypes about Black physicality that links to the historical positioning of Black “fitness” for manual labor, and has continued today through stereotypes about Black athletes, among many others.[24] The linkage of muscle mass to race has historical roots and is fundamentally rooted in racism.

If muscle mass is a key factor in calculating GFR, an estimation of muscle mass itself should be included in the equations. If it is not yet easy to measure in clinic, then we should create better tools to measure it. Race should not be crudely and harmfully used as a proxy for muscle mass.

As Dorothy Roberts explains in her TEDMED talk, “The Problem with Race-Based Medicine”:[25]

But what sense does it make for a doctor to automatically assume I have more muscle mass than [a] female bodybuilder? Wouldn’t it be far more accurate and evidence-based to determine the muscle mass of individual patients just by looking at them?…Race is a bad proxy. In many cases, race adds no relevant information at all. It’s just a distraction. Race also tends to overwhelm the clinical measures. It blinds doctors to patients’ symptoms, family illnesses, their history, their own illnesses they might have—all more evidence-based than the patient’s race. Race can’t substitute for these important clinical measures without sacrificing patient well-being.

Finally, the racial adjustment factor in GFR estimates can also be directly harmful to patients of color through psychological impacts. “Separating out one ethnic group from the general population on a laboratory slip” can lead to stigma and other interpersonal or internal forms of racism, as well as potentially delaying diagnoses.[26] The psychological impact of false-positive tests is routinely discussed in the usefulness of screening tests for cancer, and although the GFR adjustment is a question of “false-negative,” every clinical field should be held to the same standard to “do no harm” through the psychological impact of how test results are displayed and discussed.[27]

As medical students, we are taught to follow the CKD diagnosis algorithms, which hide much of the reliance of race in GFR calculations, and we are implicitly taught to accept that Black patients simply have a higher disease burden. However, the reality of this is a direct repercussion of using race as an inappropriate heuristic, one that has dire health consequences for Black patients.