Data analysis from a recent clinical trial has indicated that removing a race-based adjustment in the estimation of patients’ kidney function had a small but potentially important impact on the inclusion of participants—with differing effects on Black and non-Black participants also being observed. The analysis’ researchers, whose findings are published in the Clinical Journal of the American Society of Nephrology (CJASN), found that removal of the race-based adjustment influenced inclusion parameters too, such as severity of kidney function impairment at baseline, as well as their risk of developing cardiovascular- and kidney-related outcomes.
Current methods for estimating an individual’s kidney function, which use a patient’s estimated glomerular filtration rate (eGFR), are derived from serum creatinine levels. The most commonly used eGFR equation dates back to 2009 and includes an adjustment for Black versus non-Black race—resulting in higher eGFR values for Black patients compared to non-Black patients.
However, several healthcare institutions no longer report eGFR with an adjustment for Black race, with University of Maryland Medicine (Baltimore, USA) announcing it would eliminate the race-related component from its eGFR estimates last year. A joint taskforce fronted by the American Society of Nephrology (ASN) and the National Kidney Foundation (NKF) also recently endorsed the idea that race modifiers should not be included in equations to estimate kidney function, and published a report outlining this in the Journal of the American Society of Nephrology. However, as the authors of the more recent CJASN study note, when it comes to clinical trials, the impact of including or excluding race in these equations is currently “unclear”.
“Two solutions have been suggested. The first was the use of 2009 CKD-Epi [chronic kidney disease epidemiology collaboration] equation without the race coefficient,” said David Charytan (NYU Grossman School of Medicine, New York City, USA), lead author of the CJASN study. “More recently, ASN recommended use of a new, completely recalculated equation, the 2021 CKD-Epi creatinine equation, that does not include race and redistributes the coefficients to more equitably distribute any inequalities in the accuracy of estimates across racial categories.”
Charytan and his colleagues designed a study to evaluate the impact of including versus excluding race in eGFR equations on screening, recruitment and outcomes of clinical trials. The team evaluated the inclusion and outcomes of participants in the CREDENCE (Canagliflozin and renal events in diabetes with established nephropathy clinical evaluation) trial—which randomised individuals with type 2 diabetes and CKD to receive the drug canagliflozin, or placebo—after calculating eGFR using the 2009 CKD-Epi with and without a race-specific coefficient, or the 2021 CKD-Epi equation that contains parameters for age, sex, and serum creatinine, but does not contain a coefficient for race.
In CJASN, Charytan and colleagues relay that treatment effects were estimated using proportional hazards models and piecewise linear mixed effects models for eGFR slope. Of 4,401 randomised patients in the CREDENCE trial, they further detail, 2,931 (67%) were white, 224 (5%) were Black and 877 (20%) were Asian. Some of the key findings of their analysis were as follows:
- Among randomised participants, recalculation of screening eGFR using the 2009 CKD-Epi equation without a race-specific coefficient had no impact on the likelihood of non-Black participants meeting inclusion criteria to enrol in the trial, but would have excluded 10% of randomised Black participants for low eGFR.
- Use of the 2021 CKD-Epi equation would have excluded 4% of Black participants for low eGFR and 0.4% for high eGFR, as well as 0.7% and 7% of non-Black participants for low and high eGFR respectively.
- A high proportion of trial endpoints (cardiovascular- and kidney-related outcomes) in Black participants occurred in individuals who would have been excluded following recalculation using the race-free 2009 CKD-Epi equation—but not with the 2021 CKD-Epi equation.
- Cardiovascular and kidney treatment effects remained consistent across eGFR categories following recalculation with either equation. Changes in estimated treatment effects on eGFR slope were “modest” yet qualitatively larger following recalculation using the 2021 equation. However, the effect of canagliflozin on chronic change in eGFR was attenuated by 7% among Black participants and increased 6% in non-Black participants.
“Our analysis of CREDENCE demonstrates that removing the race-specific coefficient in the estimation of eGFR has a small but potentially important impact on the inclusion of participants in kidney disease trials,” said Charytan. “We also found that there were small effects on the severity of kidney function impairment at baseline and the risk of developing cardiovascular and kidney outcomes among enrolled participants after eGFR recalculation. These effects should be considered in terms of interpretation and design of clinical trials as we move to wider implementation of the new equation.”