Removing race and body surface area indexation for estimated kidney function based drug dosing: Aminoglycosides as justification of these principles.

Abstract

The use of race in medicine can contribute to health inequity. Updated equations for estimated glomerular filtration rate (eGFR) without race have been published. Likewise, de-indexation of eGFR to body surface area (BSA) has been recommended by regulatory guidance for drug dosing in renal impairment. Clinical data justifying these recommendations for drug dosing are sparse. We examined the gain or loss of precision in drug dosing with estimated creatinine clearance (eCLcr) and eGFR using serum creatinine (eGFRcr) with and without race and BSA indexation by evaluating the population pharmacokinetics of the aminoglycosides as a classic drug class to probe kidney function. Medical records from adult patients treated with gentamicin or tobramycin over a 13-year period were queried. Population pharmacokinetic analyses were performed using a 1-compartment base structural model. Models compared body size descriptors as covariates of the volume of distribution (V). Estimated creatinine clearance and eGFRcr using multiple contemporary equations with and without BSA indexation were tested as covariates of clearance (CL). The final data set included 2968 patients treated with either gentamicin (20.2%) or tobramycin (79.8%). Patients self-identified as Caucasian (82%), African-American (10%), or other. The median [5th, 95th percentile] weight and BSA were 80.5 [49.4, 136]kg and 1.94 [1.48, 2.56]m2 , respectively. Models of eCLcr and eGFRcr without indexation to BSA had a better model fit than eGFRcr indexed to BSA for aminoglycoside CL. The 2021 Chronic Kidney Disease Epidemiology collaboration (CKD-EPI) eGFRcr equation (no race, no BSA indexation) provided a comparable model fit to the 2009 CKD-EPI eGFRcr equation (with race, no BSA indexation) for aminoglycoside CL. Race is not a relevant covariate of aminoglycoside CL. The 2021 CKD-EPI eGFR equation without race and BSA indexation is a better method for gentamicin and tobramycin CL estimation. Confirmation of these results for other drugs can support the harmonization of dosing by kidney function.