Impact of using different renal function estimation equations on vancomycin dosing

To assess which of the formulae for estimating renal function (Cockcroft-Gault (CG), Chronic Kidney Disease Epidemiology Collaboration CKD-EPI) and Modification of Diet in Renal Disease (MDRD)) provides the most accurate prediction of minimum vancomycin concentration (Cmin) and to evaluate whether they can be interchanged to optimise vancomycin dosage.

An observational and retrospective study was undertaken in hospitalised adult patients treated with intravenous vancomycin. Patients with serum creatinine (Scr) >2 mg/dL and <0.5 mg/dL, body mass index >40 kg/m², need for extracorporeal clearance techniques and unstable renal function were excluded. Bayesian analysis was used to obtain individual pharmacokinetic parameters. Vancomycin clearance (CLvan) was calculated by means of CG (eCLvan_CG), CKD-EPI (eCLvan_CKD-EPI) and MDRD (eCLvan_MDRD) and used to obtain Cmin estimates (eCmin). eCmin and observed Cmin were compared using an intraclass correlation coefficient (ICC). A post-hoc analysis by subgroups (age, sex, weight, Scr and estimated glomerular filtration rate (eGFR)) was performed. From each eCLvan, the area under the curve (AUC) was calculated and categorised as AUC <400 mg*hour/L, AUC 400-600 mg*hour/L and AUC >600 mg*hour/L. The kappa coefficient was applied to study AUC concordance.

A total of 228 patients (69.3% men) were included. eCmin_CG had a statistically significant better agreement with Cmin (ICC >0.7) and showed good agreement in almost all subgroups. Patients with Scr >1.1 mg/dL were the only subgroup in which eCmin_MDRD and eCmin_CKD-EPI had an adequate ICC with no statistically significant differences compared with eCmin_CG. eCmin_MDRD had a similar ICC to eCmin_CG in the eGFR <60 mL/min and age 46-75 years subgroups. Kappa values showed regular agreement in all subgroups: 0.32 (AUC <400 mg*hour/L), 0.24 (AUC 400-600 mg*hour/L) and 0.41 (AUC >600 mg*hour/L).

The CG formula provides the most accurate prediction of vancomycin Cmin. In patients with eGFR <60 mL/min and aged 46-75 years, MDRD also shows a good predictive capacity. However, in low weight and elderly patients, Cmin predictions are superior with CG. Therefore, renal function estimation equations should not be considered interchangeable for vancomycin dose adjustments.