Modeling Kinetic Glomerular Filtration Rate in Adults with Stable and Unstable Kidney Function: Vancomycin as the Motivating Example

Abstract

Background Equations used to estimate kidney function for drug dosing rely on the assumption of homeostasis to translate a single‐point measurement of serum creatinine into clearance (CL). Our objective was to rank order the performance of alternate kidney function equations as predictors of drug CL in stable and unstable patients. Methods Data were extracted from medical records at a single center for all adult patients treated with vancomycin over a 5‐year period for population pharmacokinetic analysis. This analysis focused on comparison of nine kidney function equations as covariates of vancomycin CL. Both body surface area (BSA) indexed (ml/min/1.73 m2) and unindexed units (ml/min) of kidney function were tested, as time‐varying and time‐invariant covariates of vancomycin CL. Results The final data set consisted of 2640 patients (62% male, 81% white) with 6628 concentration measurements. The median (5th, 95th percentile) of measurements per patient, age, weight, body mass index (BMI) was 2 (1, 7) concentrations, 61.5 (28, 83) years, 90.0 (56.7, 147) kg, and 30.0 (20.7, 48.0) kg/m2. Unstable kidney function was documented in 43.6% of patients, primarily as acute kidney injury (AKI) on admission with improvement (19.4%) and AKI during the admission (17.4%). Models based on time‐varying kidney function estimates performed better than as time‐invariant. Kidney function estimated by the Chen method was ranked higher than other estimation methods. Conclusions A time‐varying kinetic estimated glomerular filtration rate method not indexed to BSA was identified as the highest ranked covariate model of vancomycin CL.

Comparison of Race‐Based and Non–Race‐Based Equations for Kidney Function Estimation in Critically Ill Thai Patients for Vancomycin Dosing

“…Central to this limitation is the recognition that eGFR and eCrCL equations are based on the assumption of homeostasis in creatinine production and elimination that allows for translation of a single steady‐state measurement of SCr to CL. This assumption may be false in many patients with acute infections 15 . Studies have shown that alternate kinetic functions of eGFR such as the Chen model and Chiou model are better than time‐invariant models of vancomycin CL 15,28,29 .…”

“…This assumption may be false in many patients with acute infections. 15 Studies have shown that alternate kinetic functions of eGFR such as the Chen model and Chiou model are better than timeinvariant models of vancomycin CL. 15,28,29 We did not have the data available to us in this study to explore this major point.…”

“…While discussions have focused on Black and non‐Black populations, less attention has been drawn to unique Asian populations such as the Thai 14 . A systematic evaluation of vancomycin CL prediction using eCrCL and eGFR equations, body surface area (BSA) indexed and unindexed values, and inclusion and exclusion of race has not been performed 15 …”

“…14 A systematic evaluation of vancomycin CL prediction using eCrCL and eGFR equations, body surface area (BSA) indexed and unindexed values, and inclusion and exclusion of race has not been performed. 15 The objectives of this study were to rank the performance of race-based and non-race-based equations for kidney function estimation as covariates and to evaluate the influence of covariates on PK parameters of vancomycin in critically ill Thai patients. We also quantify the marginal loss and gain with the use of alternate eGFR equations for vancomycin dosing in critically ill Thai patients.…”

Creatinine Assessment in Non–Steady-State Conditions: A Critical Review

“…Table 2 describes the studies evaluating the KeGFR approach in critically ill patients, a population with frequently changing kidney function. 15,21-26 All the studies based the KeGFR calculations on the method of Chen. 10 Based on the results of these investigations, we suggest that standard methods be used when SCr is stable with only minor fluctuation.…”