Removing Race From Chronic Kidney Disease-Epidemiology Collaboration Equation Could Result in Undertreatment of Black Individuals

After removing race from the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation, investigators reported that Black patients received a lower estimated glomerular filtration rate (eGFR), thus excluding them from receiving anticancer therapies and resulting in undertreatment, according to a retrospective analysis of the National Cancer Institute’s phase 1 clinical trial participant data published in Lancet Oncology.

Black patients more frequently received the recommendation to either be given reduced doses of treatment or were considered ineligible for treatment entirely when CKD-EPI without race was utilized as opposed to CKD-EPI alone. When CKD-EPI was utilized, use of cisplatin increased by 72%, pemetrexed use increased by 120%, bendamustine use increased by 67%, and capecitabine use increased by 150%. Additionally, the use of etoposide increased by 150%, topotecan use increased by 67%, fludarabine use by 61%, and bleomycin use by 163%.

“Removal of race from the CKD-EPI equation results in estimates of GFR that will change care for Black patients with cancer by excluding more patients from receiving full doses of potentially life-saving therapy, which could adversely affect survival outcomes,” the study authors wrote. “Exclusion of the race term from the CKD-EPI equation could paradoxically worsen care for Black patients with cancer. Although guidance on implementation of new, race-agnostic methods of kidney function assessment is forthcoming, the timeline for widespread clinical implementation is unclear and omission of race from the CKD-EPI equation in the interim could negatively affect care for Black patients with cancer.”

Eligibility criteria for the analysis were trial specific and ensured that patients were suitable for participation in phase 1 trials. Some criteria included a serum creatinine concentration of 1.5 mg/dL or lower, as well as eClCr of 60 mL per minute or higher, and an ECOG performance status of 0 or 1. The dataset included factors such as demographic information, physical measurements, and pretreatment serum creatinine values.

Kidney function was estimated utilizing eGFR based on creatine, which was calculated with the 2009 CKD-EPI equation both with and without race, as well as calculating eClCr with the Cockcroft-Gault equation. Additionally, a simulation was conducted in order to compare dosing and eligibility recommendations for several anti-cancer therapies based on eGFRCr, as calculated by CKD-EPI and CKD-EPI without race, as well as eClCr calculated by Cockcroft-Gault. Drugs with kidney function–based eligibility cut off included cisplatin at less than 60 mL per minute, pemetrexed at less than 45 mL per minute, bendamustine at less than 40 mL per minute, and mitomycin at less than 30 mL per minute.

The retrospective analysis included 4118 patients who enrolled from January 1995 through October 2010. Nine percent of the population was Black. The patient subgroup had a median age of 57 years (interquartile range [IQR], 47-64), a median height of 170.0 cm (IQR, 162.6-177.4), a median body weight of 78.1 kg (IQR, 67.0-89.8), median body surface area of 1.91 m2 (IQR, 1.77-2.09), and serum creatinine concentration of 0.9 mg/dL (0.8-1.1).

The proportions of patients with eGFR or eClCr of less than 90 mL/min and less than 60 mL/min included 32% and 7% for the CKD-EPI cohort, 51% and 13% for the CKD-EPI without race cohort, and 49% and 13% for the Cockcroft-Gault cohort. When CKD-EPI was utilized, 26% of patients were reclassified to a more severe chronic kidney disease stage compared with CKD-EPI. Additionally, 10% of patients were reclassified to a more severe chronic kidney disease stage and 8% were reclassified into a less severe disease stage when the use of CKD-EPI without race was compared with Cockcroft-Gault.

The proportion of individuals who were unable to receive treatment ranged from 7% to 13% for cisplatin, 1% to 3% for pemetrexed, 1% to 1% for bendamustine, and 0% to 1% for mitomycin, and depended on how kidney function was calculated. Eligibility discordance between CKD-EPI and CKD-EPI without race ranged from 1% to 5% of patients as well as less than 1% to 5% when comparing Cockcroft-Gault and CKD-EPI without race.

The proportion of patients who were recommended to have a renal-based reduction in treatment dose ranged from 0% to 1% for oxaliplatin, 3% to 7% for capecitabine, 3% to 7% for etoposide, 1% to 1% for topotecan, 22% to 35% for fludarabine, and 2% to 6% for bleomycin, and depended on how kidney function was calculated. Additionally the number of patients who were recommended to undergo a renal dose adjustment when using CKD-EPI without race vs with race increased from 0 patients to 2 patients for oxaliplatin, 150% for capecitabine, 150% for etoposide, 67% for topotecan, 61% for fludarabine, and 163% for bleomycin.

Reference

Casal MA, Ivy SP, Beumer JH, et al. Effect of removing race from glomerular filtration rate-estimating equations on anticancer drug dosing and eligibility: a retrospective analysis of National Cancer Institute phase 1 clinical trial participants. 2021;22(9):1333-1340. doi:10.1016/S1470-2045(21)00377-6