Vancomycin and the Risk of AKI: A Systematic Review and Meta-Analysis

Abstract

Background and objectives: Vancomycin has been in use for more than half a century, but whether it is truly nephrotoxic and to what extent are still highly controversial. The objective of this study was to determine the risk of AKI attributable to intravenous vancomycin.

Design, setting, participants, & measurements: We conducted a systematic review of randomized, controlled trials and cohort studies that compared patients treated with intravenous vancomycin with a control group of patients given a comparator nonglycopeptide antibiotic and in which kidney function or kidney injury outcomes were reported. PubMed and Cochrane Library were searched from 1990 to September of 2015. Two reviewers extracted data and assessed study risk of bias, and one reviewer adjudicated the assessments. A meta-analysis was conducted on seven randomized, controlled trials (total of 4033 patients).

Results: Moderate quality evidence suggested that vancomycin treatment is associated with a higher risk of AKI, with a relative risk of 2.45 (95% confidence interval, 1.69 to 3.55). The risk of kidney injury was similar in patients treated for skin and soft tissue infections compared with those treated for nosocomial pneumonia and other complicated infections. There was an uncertain risk of reporting bias, because kidney function was not a prespecified outcome in any of the trials. The preponderance of evidence was judged to be indirect, because the majority of studies compared vancomycin specifically with linezolid.

Conclusions: Our findings suggest that there is a measurable risk of AKI associated with vancomycin, but the strength of the evidence is moderate. A randomized, controlled trial designed to study kidney function as an outcome would be needed to draw unequivocal conclusions.

Keywords: Anti-Bacterial Agents; Cohort Studies; Control Groups; Cross Infection; Glycopeptides; Humans; Libraries; Linezolid; Pneumonia; PubMed; Randomized Controlled Trials as Topic; Risk Assessment; Soft Tissue Infections; Vancomycin; acute kidney injury; chronic renal insufficiency; meta-analysis.

Figure 1.

Summary of evidence search and selection. RCT, randomized, controlled trial.

Figure 2.

Forest plot of included randomized, controlled trials. Risk ratios (RRs) and 95% confidence intervals (95% CIs) are shown for each study and the pooled analysis using a fixed effects model and the Mantel–Haenszel method. RR>1.0 means that the risk of kidney injury in the vancomycin group is greater than that in the control group.

Figure 3.

Funnel plot of included randomized, controlled trials. Risk ratio (RR) is plotted against SEM. Dotted lines indicate the pooled effect estimate and 95% confidence intervals. Studies with high risk of bias are shown as gray circles, and studies with uncertain risk of bias are shown as white circles.