Related Experiment Video
Updated: Aug 20, 2025
A Large Animal Model for Acute Kidney Injury by Temporary Bilateral Renal Artery Occlusion
Published on: February 2, 2021
Removing race and body surface area indexation for estimated kidney function based drug dosing: Aminoglycosides as
Manjunath P Pai1, Sirima Sitaruno2, Mohamed Abdelnabi1
1Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, Michigan, USA.
Study Objective:
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.
Design:
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).
Main Results:
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.
Conclusions:
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.
Related Concept Videos
01:11Renal Failure: Dose Adjustments
Reduced renal clearance and elimination rate are common outcomes of renal impairment. These alterations lead to a prolonged elimination half-life and an altered apparent volume of distribution for drugs. As a result, dosage adjustments are typically necessary to maintain optimal drug levels in the body.
However, dosage adjustments...
01:17Factors Affecting Renal Clearance: Renal Impairment
One condition associated with renal failure is uremia. Uremia is characterized by impaired glomerular filtration and fluid accumulation in the body. This condition hinders the renal clearance of drugs, resulting in drug accumulation and potential...
01:08Renal Drug Clearance: Comparison Between Renal Excretion Methods
Renal clearance is often associated with the renal glomerular filtration rate (GFR), which represents the rate at which plasma is filtered through the glomeruli in the kidney. When drug reabsorption is minimal and there is no active secretion, renal clearance is closely related to the...
01:06Renal Drug Clearance: Overview
Renal clearance can be calculated using different methods. One approach is to divide the urinary drug excretion rate by the plasma drug concentration. This method directly measures renal clearance, indicating the kidneys' efficiency in...
01:07Determination of Renal Drug Clearance: Graphical and Midpoint Methods
The graphical method involves plotting the rate of drug excretion in urine against the plasma drug concentration. By analyzing the graph, the clearance can be calculated and obtained. Drugs rapidly excreted by the kidneys exhibit a...
01:11One-Compartment Open Model: Urinary Excretion Data and Determination of k