An Evaluation of the Incidence of Nephrotoxicity After a Loading Dose of Vancomycin in Patients With Severe Renal Impairment

Background: Loading doses of vancomycin assist in the rapid achievement of target trough concentrations. Patients with renal dysfunction have been excluded from studies evaluating loading doses.

Objective: The purpose of this study was to investigate nephrotoxicity related to initial vancomycin dose in patients with severe renal dysfunction.

Methods: A retrospective cohort study was approved by the Institutional Review Board of a large, academic health system. Adults were included if they received intravenous vancomycin in the emergency department and presented with creatinine clearance < 30 mL/min. Chronic dialysis patients were excluded. The primary outcome was incidence of nephrotoxicity after an initial high (>20 mg/kg) vs. low (≤20 mg/kg) dose of vancomycin. Secondary outcomes included dialysis, vancomycin concentrations, length of stay, in-hospital mortality, and a composite outcome of nephrotoxicity or dialysis.

Results: Of the 927 patients included in the analysis, nephrotoxicity occurred in 7.2% and 13.8% of patients in the high- and low-dose groups, respectively (p < 0.01). Patients in the high-dose group had a reduced risk of nephrotoxicity (relative risk 0.53; 95% confidence interval 0.35-0.78). The reduction in risk remained after fitting a generalized linear model adjusting for weight, age, sex, initial serum creatinine, diabetes, and chronic kidney disease (relative risk 0.61; 95% confidence interval 0.39-0.93). Limitations of this study include its retrospective design and single-center population.

Conclusion: These data suggest that vancomycin loading doses do not increase nephrotoxicity compared with lower doses in patients with severe renal dysfunction. These patients should be included in future studies relating to vancomycin loading doses.