Vancomycin area under the curve versus trough only guided dosing and the risk of acute kidney injury: Systematic review and meta-analysis

Abstract

Vancomycin is commonly used to treat methicillin-resistant Staphylococcus aureus infections and is known to cause nephrotoxicity. Previous Vancomycin Consensus Guidelines recommended targeting trough concentrations but the 2020 Guidelines suggest monitoring vancomycin area under the curve (AUC) given the reduced risk of acute kidney injury (AKI) at similar levels of efficacy. This meta-analysis compares vancomycin-induced AKI incidence using AUC-guided dosing strategies versus trough-based monitoring. Literature was queried from Medline (Ovid), Web of Science, and Google Scholar from database inception through November 5, 2021. Interventional or observational studies reporting the incidence of vancomycin-induced AKI between AUC- and trough-guided dosing strategies were included. In the primary analysis, the Vancomycin Consensus Guidelines definition for AKI was used if reported; otherwise, the Risk, Injury, and Failure; and Loss, and End-stage kidney disease (RIFLE) or Kidney Disease Improving Global Outcomes (KDIGO) definitions were used. The incidence of nephrotoxicity was evaluated between the two strategies using a Mantel-Haenszel random-effects model, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Subgroup analyses for adjusted ORs and AKI definitions were performed. Heterogeneity was identified using Cochrane's Q test and I² statistics. A total of 10 studies with 4231 patients were included. AUC-guided dosing strategies were associated with significantly less vancomycin-induced AKI than trough-guided strategies [OR 0.625, 95% CI (0.469-0.834), p = 0.001; I² = 25.476]. A subgroup analysis of three studies reporting adjusted ORs yielded similar results [OR 0.475, 95% CI (0.261-0.863), p = 0.015]. Stratification by AKI definition showed a significant reduction in AKI with the Vancomycin Consensus Guidelines definition [OR 0.552, 95% CI (0.341-0.894), p = 0.016] but failed to find significance in the alternative definitions. Area under the curve-guided dosing strategies are associated with a lower incidence of vancomycin-induced AKI versus trough-guided dosing strategies (GRADE, low). Limitations included the variety of AKI definitions and the potential for confounding bias.

Keywords: acute kidney injury; area under the curve; nephrotoxicity; trough; vancomycin.

FIGURE 1

PRISMA diagram. Summary of evidence search and selection. AUC, area under the curve.

FIGURE 2

Forest plot examining incidence rate of AKI reported as odds ratio (OR). The overall meta‐analysis compares AKI incidence of AUC‐guided and trough‐guided dosing. AKI, acute kidney injury; AUC, area under the curve; CI, confidence interval.

FIGURE 3

Funnel plot for all included studies. The funnel plot including all studies to visualize risk of bias in the overall analysis.

FIGURE 4

Forest plot examining effects of adjusting for confounders on AKI incidence. Subgroup analysis includes studies reporting adjusted odds ratios. AUC, area under the curve; CI, confidence interval.

FIGURE 5

Forest plot examining the effect of different AKI definitions on AKI incidence. The forest plots present the results of the subgroup analyses by AKI definition. Panel A—RIFLE; Panel B—AKIN; Panel C—Vancomycin Consensus Guidelines; Panel D—KDIGO. AKI, acute kidney injury; AKIN, Acute Kidney Injury Network; AUC, area under the curve; CI, confidence interval; KDIGO, Kidney Disease Improving Global Outcomes; MH, Mantel–Haenszel; RIFLE, Risk, Injury, Failure, Loss, End‐stage kidney disease.

FIGURE A1

This figure shows the results of a sensitivity analysis performed excluding Lines et al., due to its high risk of bias. AUC, area under the curve; CI, confidence interval; MH, Mantel–Haenszel.