Removing race-specific coefficient in eGFR equation impacts CKD trial inclusion
Removing the race-specific coefficient from the equation that determines eGFR results in a “small but potentially important” effect on the inclusion of patients in [chronic kidney disease] trials, according to published data.
Further, removing the race-specific coefficient impacts the underlying risk of kidney and cardiovascular events that change depending on the eGFR equation used.
“Incorporation of race into the CKD-Epi1 eGFR equation has generated significant attention. In particular, a race-specific coefficient results in higher eGFR amongst Black individuals,” David M. Charytan, MD, MSc, a nephrologist at NYU Langone Medical Center in New York, and colleagues wrote. “To understand the potential impact of its elimination on both the inclusion of Black participants in and the results of CKD trials, we analyzed data from the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation Trial (CREDENCE), which demonstrated that canagliflozin prevented kidney and cardiovascular outcomes in patients with type 2 diabetes and CKD.”
The CREDENCE trial randomized 4,401 patients (67% were white; 5% were Black; 20% were Asian) with type 2 diabetes and CKD to treatment with either canagliflozin or placebo. Charytan and colleagues analyzed the trial outcomes after determining eGFR using the 2009 CKD-Epi creatinine equation with and without a race-specific coefficient or the 2021 CKD-Epi creatinine equation.
Using proportional hazards models and piecewise linear mixed-effect models for eGFR slope, researchers determined treatment effects.
The recalculation of screening eGFR using the 2009 equation without a race-specific coefficient revealed no effect on the probability of patients who were not Black meeting inclusion criteria. However, it would have excluded 10% of the randomized Black patients for eGFR. Similarly, the recalculation with the 2021 equation would have excluded 4% of Black patients for low and 0.4% for high eGFRs in addition to 0.7% and 7% of patients who were not Black for low and high eGFRs.
Additional findings include the large proportion of trial endpoints, such as cardiovascular and kidney-related outcomes, in Black patients that took place in those who would have been excluded after recalculation using the race-free 2009 CKD-epi equation but not with the 2021 CKD Epi-equation. Regardless of the equation used, cardiovascular and kidney treatment effects stayed similar across eGFR categories.
“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. 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,” Charytan said in a press release. “These effects should be considered in terms of interpretation and design of clinical trials as we move to wider implementation of the new equation.” According to researchers, limitations of the study include international enrollment and a small number of Black patients.
How would eliminating race-based adjustments in estimates of kidney function impact clinical trials?
https://www.newswise.com/articles/how-would-eliminating-race-based-adjustments-in-estimates-of-kidney-function-impact-clinical-trials?sc=cwhr&xy=10007438. Published Jan. 19, 2022. Accessed Jan. 24, 2022.