Excluding race in kidney function estimates may impact cancer treatment for Black patients
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Removing race from estimated glomerular filtration rate equations could result in more Black patients being excluded from anticancer therapy, thus negatively affecting outcomes, according to study results published in The Lancet Oncology.
“During the past year, inclusion of race in eGFR [estimated glomerular filtration rate] equations has been questioned, prompting discussion of the consequences of both the inclusion and exclusion of race. A joint National Kidney Foundation-American Society of Nephrology task force on reassessing the inclusion of race in diagnosing kidney disease has been convened and is critically evaluating the issue,” Jan H. Beumer, PharmD, PhD, DABT, professor in the departments of pharmaceutical sciences and medicine at University of Pittsburgh and director of the Cancer Pharmacokinetics and Pharmacodynamics Facility at UPMC Hillman Cancer Center, told Healio.
“Black patients in the U.S. are disproportionately affected by cancer, as evidenced by disparities in both incidence and outcomes,” Beumer added. “Therefore, we wanted to assess the effects of excluding race in Chronic Kidney Disease-Epidemiology Collaboration-derived estimates of kidney function on patient dosing and eligibility recommendations for cancer agents with kidney function cutoffs.”
The retrospective analysis included 340 Black patients with cancer (median age, 57 years; interquartile range, 47-64; 50.6% men) included in phase 1 clinical trials between 1995 and 2010. The overall study population had a median body weight of 78.1 kg, median body surface area of 1.91 m² and median serum creatinine concentration of 0.9 mg/dL.
Researchers calculated eGFR based on creatinine by Chronic Kidney Disease-Epidemiology Collaboration equation with and without race as a consideration. They also calculated estimated creatinine clearance with the Cockcroft-Gault equation.
“We included the Cockcroft-Gault formula as a comparator because most oncologists still use this formula,” Beumer said. “The Cockcroft-Gault equation was developed in a predominantly white population and, therefore, could not include race as a covariate.”
Investigators performed dosing simulations based on assessment of kidney function for 10 different chemotherapeutic drugs with kidney function cutoffs for dosing or eligibility. They calculated the absolute proportion of patients eligible or in each renal dosing range for each cancer therapy.
Results showed median eGFR with race included of 103 mL/min, compared with 89 mL/min without race included and 90 mL/min with the Cockcroft-Gault formula.
“[Although] we know that [the Cockcroft-Gault] formula is outdated, our work confirms its poor performance and reemphasizes the need for oncologists to use more recent, better alternatives, such as the Chronic Kidney Disease-Epidemiology Collaboration equation,” Beumer said. “Arguably, the Cockcroft-Gault equation converts the higher serum creatinine in Black patients at equal kidney function into a negatively biased kidney function estimates, resulting in Black patients being inappropriately underdosed or deemed ineligible for cancer therapeutics in current clinical practice.”
Removing race from the equation approximately doubled the proportion of patients with an eGFR below the key cutoff of 60 mL/min, from 7% to 13%. Consequently, the proportion of patients ineligible to receive a cancer therapy or recommended for a dose reduction increased considerably, from 61% for fludarabine to 163% for bleomycin.
Moreover, researchers found exclusion of race from the Chronic Kidney Disease-Epidemiology Collaboration equation would result in 5% of patients having discordant recommendations for drug eligibility and 18% of patients having discordant dosage recommendations.
“Cancer therapies have a very fine line between toxicity and efficacy, and the consequences of undertreatment can be fatal. Removing race from [the equation] will deem more Black patients with cancer ineligible to receive a reduced dose of anticancer therapies,” Beumer said.
“In addressing systemwide societal issues, we must consider consequences for the treatment of individual patients,” Beumer added. “Especially if patients have discrepant recommendations depending on whether race is included or excluded from the equation, physicians should consider eGFR in the context of other factors including treatment intent (whether curative or not), presence of any comorbidity, performance status, etc. and not as a single treatment criterion.”
Future research will examine the performance of the Cockcroft-Gault and Chronic Kidney Disease-Epidemiology Collaboration equations in predicting eGFR and evaluating which demographic factors — including race — are important to consider in these predictions, Beumer said.
“[Although] this trial is accruing rapidly, we will need to ensure that we have an adequate representation of Black patients in our study population to better quantitate the impact of race on kidney function estimates among patients with cancer,” Beumer said.
Removing race from eGFR serum creatinine equations will reduce accuracy because omission of an exploratory variable from an estimation equation creates systematic error in the subgroups defined by the variable, Andrew S. Levey, MD, professor of medicine and chief emeritus of the William B. Schwartz division of nephrology at Tufts Medical Center, and Neil R. Powe, MD, MPH, MBA, leader of the University of California, San Francisco Medicine Service at Priscilla Chan and Mark Zuckerberg San Francisco General Hospital, wrote in an accompanying editorial.
“Balancing considerations of accuracy and equity among the alternative methods is challenging,” Levey and Powe wrote. “The consistency of estimated and measured values, limitations of each value and patients’ clinical characteristics must be considered for clinical decision-making. More frequent use of confirmatory tests for GFR evaluation will increase efforts and cost but it will promote appropriate decisions and prevent disparities in cancer treatment.”
References:
Casal MA, et al. Lancet Oncol. 2021;doi:10.1016/S1470-2045(21)00377-6.
Levey AS and Powe NR. Lancet Oncol. 2021;doi:10.1016/S1470-2045(21)00391-0.
For more information:
Jan H. Beumer, PharmD, PhD, DABT, can be reached at UPMC Hillman Cancer Center, Research Pavilion, Suite G.27e, 5117 Centre Ave., Pittsburgh, PA 15213; email: beumerjh@upmc.edu.
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