Aims: Accurately estimating kidney function is essential for the safe administration of renally cleared drugs such as ganciclovir. Current practice recommends adjusting renally eliminated drugs according to the Cockcroft-Gault equation. There are no data on the utility of the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in ganciclovir dosing. To evaluate which renal function equation best predicts ganciclovir clearance.
Methods: The performance of the Cockcroft-Gault equation, isotope dilution mass spectrometry (IDMS)-traceable 4-variable MDRD study (MDRD4-IDMS) equation and CKD-EPI equation in determining ganciclovir clearance were assessed retrospectively in patients treated with ganciclovir from 2004-2015. The MDRD4-IDMS and CKD-EPI equations adjusted to individual body surface area (MDRD4-IDMS·BSA and CKD-EPI·BSA, respectively) were also evaluated. Patients with intravenous ganciclovir peak and trough concentrations in their medical records were included in the study. Ganciclovir clearance was calculated from serum concentrations using a one-compartment model. The five equations were compared based on their predictive ability, the coefficient of determination, through a linear regression analysis. The results were validated in a group of patients.
Results: One hundred patients were included in the final analysis. Seventy-four patients were analysed in the learning group and 26 in the validation group. The coefficient of determination was 0.281 for Cockcroft-Gault, 0.301 for CKD-EPI·BSA, 0.308 for MDRD4-IDMS·BSA, 0.324 for MDRD4-IDMS and 0.360 for CKD-EPI. Subgroup analysis also showed that CKD-EPI is a better predictor of ganciclovir clearance. Analysis of the validation group confirmed these results.
Conclusions: The CKD-EPI equation correlates better with ganciclovir clearance than the Cockcroft-Gault and MDRD4-IDMS equations, even the clinical difference between the equations is scarce.
Keywords: CKD-EPI equation; Cockcroft-Gault equation; MDRD study equation; clearance; ganciclovir; renal dosage adjustments.
© 2018 The British Pharmacological Society.