The History of Race in Estimated GFR Equations

Glomerular filtration rate (GFR) is a measure of the kidney’s ability to filter substances and excess fluid out of the blood into the urine and is a factor in the diagnosis and staging of chronic kidney disease (CKD) (1). The process of obtaining a patient’s actual GFR is long, tedious, and not widely utilized, and the majority of GFR measurements are estimated. These estimates are calculated using equations that account for the patient’s age, sex, weight, and the amount of a waste product known as creatinine in the blood (2). The first of these equations, the Cockcroft and Gault formula, was developed in 1973 and was originally devised to estimate creatinine clearance. The Cockcroft Gault formula is as follows:

 

CCr={((140–age) x weight)/(72xSCr)}x 0.85 (if female)

where:

CCr (creatinine clearance) = mL/minute

Age = years

Weight = kg

SCr (serum creatinine) = mg/dL

 

However, there are multiple caveats to this calculation. First, the equation was formulated using the data from a sample of 249 men; second, it does not use standardized creatinine values; and third, it does not account for body surface area. As such, questions about the accuracy of GFR estimations and generalizability to all patients arose (3). Since the first Cockcroft Gault formula, there have been several studies and iterations of formulas published to more accurately estimate GFR based on patient-specific factors.

 A landmark study from 1999 was the first to propose a race coefficient for black patients based on the conclusion “that on average, black persons have greater muscle mass than white persons.” This conclusion was based on the results of three small studies published between 1970 and 1999. The first study compared the body composition of approximately 240 white and black children and found that, on average, black children had lower body fat and different body densities. The second study collected data from approximately 40 adults and concluded that black adults had higher total body potassium and calcium levels compared to white adults. Finally, the third study found that of 60 healthy hospital workers, black employees had higher average serum creatinine kinase levels (4). These assumptions persisted and continued through later iterations of the formula despite the limitations and small sample size of the studies.

The addition of the race coefficient introduced new potential biases. Providers might have two identical patients in sex, age, height, weight, and creatinine levels, but the black patient would have a higher estimated kidney function compared to the white patient based on the equation’s estimate. This possible overestimation of kidney function in black patients may lead to a decrease in the diagnosis of CKD, inaccurate staging of CKD, fewer nephrologist referrals, delays in the initiation of dialysis, and fewer eligible kidney transplant recipients. According to the US Renal Data System (USRDS) 2018 Annual Report, African Americans in older age groups experienced higher rates of CKD compared to white Americans of similar age (5). The Jackson Heart Study, an epidemiologic study of African Americans in Mississippi, also found the rate of CKD in this population to be close to 20%. African Americans were found to have a 2.9 times increased risk for end-stage kidney disease (ESKD) compared to white Americans in 2016. It also reported that black patients with ESKD exhibit a lower rate of kidney transplant compared to persons of other races (6). Without the inclusion of a race coefficient in estimations of GFR, the incidence and severity of CKD and in the African American population may be even higher than reported.

Overall, there was relatively little opposition of the black race coefficient by physicians and medical institutions until Beth Israel Deaconess Medical Center in Boston, Massachusetts removed the race factor from their GFR estimations in 2017 (7). Other hospitals and universities started to follow suit in the following years, and in July of 2020 the National Kidney Foundation (NKF) and American Society of Nephrology (ASN) formed a joint task force to review the use of race in estimated GFR calculations (8). The final report of the task force was published in September 2021, which recommended the use of the 2021 CKD-EPI creatinine equation that estimates kidney function without using race (9). The 2021 CKD-EPI creatinine equation is as follows:

 

eGFRcr = 142 x min(Scr/κ, 1)α x max(Scr/κ, 1)-1.200 x 0.9938Age x 1.012 [if female]

where:

Scr = standardized serum creatinine in mg/dL

κ = 0.7 (females) or 0.9 (males)

α = -0.241 (female) or -0.302 (male)

min(Scr/κ, 1) is the minimum of Scr/κ or 1.0

max(Scr/κ, 1) is the maximum of Scr/κ or 1.0

Age (years)

 

It is also recommended that the measurement of Cystatin C levels, a blood waste product similar to creatinine, be more widely applied for GFR calculations, as it shows less bias by race compared to equations that use creatinine levels alone (9).

Although the removal of the race coefficient for estimated GFR calculations may seem like a minor adjustment in the context of the American medical system, this change could create large impacts on treatment decisions in patients with CKD. According to upcoming projections made in the Journal of the American Society of Nephrology, the use of the 2021 CKD-EPI equation may result in substantial changes to recommended care for patients of all racial and ethnic groups. The authors estimate that 434,000 new CKD diagnoses may be assigned for African American adults. There may also be reclassification of 584,000 African American adults to more advanced stages of CKD and expansion of referrals by nephrologists for 41,800 patients. Although unintended, negative impacts of this change may also be seen. Kidney donation eligibility may be restricted to 246,000 patients, and medication doses may be decreased in 222,000 patients. Among non-black adults, CKD diagnosis may be reversed in 5.5 million patients, and almost 4.6 million patients may be reclassified to less advanced stages of CKD. These changes may also disqualify nephrologist referrals for 75,800 patients, and reverse medication dose reductions for 1.47 million patients (10).

The calculations used for estimating GFR are imperfect and must be continually reviewed and updated to better estimate patient kidney function. As the population continues to become more racially and ethnically diverse, the medical community should continue to critically evaluate and change protocols that may invite biases based on perceived differences between patient populations.

References:

  1. Papadakis MA, McPhee SJ, Rabow MW, McQuaid KR. Current Medical Diagnosis & Treatment 2023. McGraw-Hill; 2023.
  2. National Kidney Foundation. Estimated Glomerular Filtration Rate (eGFR). National Kidney Foundation. Published January 15, 2019. Accessed January 12, 2023. https://www.kidney.org/atoz/content/gfr
  3. Cockcroft-Gault Formula. National Kidney Foundation. https://www.kidney.org/professionals/kdoqi/gfr_calculatorcoc#:~:text=The%20Cockcroft%20and%20Gault%20formula
  4. Inserro A. Flawed Racial Assumptions in eGFR Have Care Implications in CKD. https://www.ajmc.com. Published October 25, 2020. Accessed January 12, 2023. https://www.ajmc.com/view/flawed-racial-assumptions-in-egfr-have-care-implications
  5. United States Renal Data System. Chapter 2: Identification and Care of Patients with CKD. In 2018 USRDS annual data report: Epidemiology of kidney disease in the United States, vol. 1. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2018.
  6. Ladenheim A, Tran N, Roshanravan B, Young B. Race and eGFR: Addressing Health Disparities in Chronic Kidney Disease. Lab Best Practice. Published April 29, 2021. Accessed January 12, 2023. https://health.ucdavis.edu/blog/lab-best-practice/race-and-egfr-addressing-health-disparities-in-chronic-kidney-disease/2021/04
  7. Hoenig MP, Mann A, Pavlakis M. Removal of the Black race coefficient from the estimated glomerular filtration equation improves transplant eligibility for Black patients at a single center. Clin Transplant. 2022;36(2):e14467. doi:10.1111/ctr.14467
  8. National Kidney Foundation. Understanding African American and non-African American eGFR laboratory results. National Kidney Foundation. Accessed January 12, 2023. https://www.kidney.org/atoz/content/race-and-egfr-what-controversy
  9. National Kidney Foundation and the American Society of Nephrology Task Force. National Kidney Foundation and the American Society of Nephrology release new way to diagnose kidney diseases. Published September 23, 2021. Accessed January 12, 2023. https://www.kidney.org/news/nkf-and-asn-release-new-way-to-diagnose-kidney-diseases#:~:text=NKF%20and%20ASN%20recommend%20diagnosing,kidney%20diseases%20in%20some%20people.
  10. Diao JA, Wu GJ, Wang JK, et al. National Projections for Clinical Implications of Race-Free Creatinine-Based GFR Estimating Equations. J Am Soc Nephrol. 2023;34(2):309-321. doi:10.1681/ASN.2022070818

GMO-000828  Rev A  03/2024