Comparing Two Equations for Estimation of Kidney Function (Cock-croft-Gault and Glomerular Filtration Rate Assessment in Liver Disease) for Vancomycin Dosing in Adult Liver Transplant Recipients: A Pilot, Randomized Clinical Trial

Abstract

Background: In the setting of impaired liver function, estimation of glomerular filtration rate (GFR) using common creatinine-based equations is inaccurate. Recently, the Glomerular filtration Rate Assessment In Liver disease (GRAIL) model has been introduced to estimate GFR in liver transplantation. This study was conducted to compare vancomycin dose adjustment in liver transplant patients using Cockcroft-Gault (C-G) versus the GRAIL method. Methods: In this pilot, randomized clinical trial, adult liver transplant recipients who were a candidate to receive intravenous vancomycin were enrolled. The level of kidney function was estimated using the GRAIL model and C-G equation in the intervention and control arms, respectively. Then, vancomycin maintenance doses were accordingly adjusted. At the steady state, peak and trough serum concentrations of vancomycin were collected for area under the concentration-time curve (AUC) calculation and pharmacokinetic comparisons. Results: Fifteen patients were enrolled in each arm of study. The mean daily dose of vancomycin was estimated insignificantly lower for individuals in the GRAIL arm than the C-G group (1550.00±544.45 mg versus 1750.00± 389.60 mg). Compared with the C-G group, a higher rate of patients in the GRAIL arm experienced below-target vancomycin trough concentrations (40.0% versus 13.3%), and a lower rate showed above target trough concentration (40.0% versus 66.7%). These differences did not reach statistical significance. Individuals in the GRAIL arm represented a significantly higher rate of below target vancomycin AUC/MIC than patients in the C-G arm (46.7% versus 6.7%) (P=0.049). No differences in clinical outcomes were observed between the two groups. Conclusion: Using the GRAIL model for vancomycin dosing may result in less percent of patients with at target AUC/MIC compared to the C-G method and expose more patients at risk for vancomycin under dosing.

Keywords

• cockcroft-gault
• drug dosing
• grail
• liver transplantation
• pharmacokinetics
• vancomycin