The Glomerular Filtration Rate Estimators in the Pharmacokinetic Modelling in Acute Kidney Injury: An Observational Study

Abstract

The glomerular filtration rate (GFR), according to which the drug dose for patients with chronic kidney disease (CKD) is adjusted, is computed with estimators (eGFR) that are developed specifically for CKD. These particular types of estimators are also used in population pharmacokinetic (pop PK) modelling in drug development. Similar approaches without scientific validation have been proposed for patients with acute kidney injury (AKI), yet it is uncertain which specific eGFR should be used for drug dosing or in pop PK models in patients with AKI. In our study, we included 34 patients with AKI and vancomycin (VCM) treatment, and we built both individual PK and pop PK (non-linear mixed-effects, one-compartment) models to see which eGFR estimator is the best covariate. In these models different eGFRs (Cockcroft-Gault, MDRD, CKD-EPI 2009, Jelliffe and Jelliffe, Chen et al., and Yashiro et al. 2013) were used. We included six additional patients to validate the final pop PK model. All eGFRs underrate the true renal clearance in the AKI, so we created pop PK models for VCM dosing in AKI with all eGFRs, to discover that the most accurate model was the one with the Cockcroft-Gault estimator. Since the eGFRs underestimate the true renal clearance in AKI, they are inaccurate for clinical drug dosing decisions, with the exception of the Cockcroft-Gault one, which is appropriate for the pop PK models intended for drug development purposes in AKI.

Acute Kidney Injury Following Coronary Artery Bypass Grafting with Cardiopulmonary Bypass at Dr. Soetomo General Academic Hospital Surabaya: A Preliminary Study

“…This formula used body weight to calculate creatinine clearance in mL/minute (21). Alteration in eGFR is connected to creatinine clearance from collected urine after 24 hours and Gentamycin clearance (22,23). A multicenter prospective study found that the Cockcroft-Gault formula could be used to predict the prognosis of a cardiovascular event, specifically mortality and bleeding (24).…”

Evaluating prediction methods for glomerular filtration to optimise drug doses in obese and nonobese patients

“…9,45 In contrast, our study represents a proof-of-concept for employing exposure data from an exclusively renally eliminated drug in both obese and nonobese individuals to evaluate predictors and prediction methods of GFR/creatinine clearance. The predictive performance of GFR/creatinine clearance prediction methods has been evaluated before via the elimination of drugs predominantly eliminated via glomerular filtration, such as vancomycin 46,47 (critically ill patients) or gentamicin 48 (geriatric patients). However, accuracy of elimination of vancomycin as GFR/creatinine clearance reference in obese and nonobese patients was compromised by tubular secretion and reabsorption.…”