Attributable Risk and Time Course of Colistin-Associated Acute Kidney Injury

Abstract

Background and objectivesDespite colistin’s longstanding reported association with nephrotoxicity, the attributable risk and timing of toxicity onset are still unknown. Whether substantial toxicity occurs during the initial 72 hours of exposure has important implications for early treatment decisions. The objective of this study was to compare colistin-exposed patients with a matched control group given other broad spectrum antibiotics.Design, setting, participants, & measurementsWe conducted a retrospective cohort study in patients treated for multidrug-resistant Pseudomonas, Klebsiella, or Acinetobacter spp. Colistin-exposed patients were matched to unexposed controls using propensity scores. AKI was defined according to the Kidney Disease Improving Global Outcomes creatinine criteria. Incidence rate ratios and risk differences of AKI in the matched cohort were estimated with the generalized estimating equation Poisson regression model. Risk factors for AKI were tested for effect modification in the matched cohort.ResultsThe study included 150 propensity-matched pairs with similar types of infection, similar delays to effective treatment, and similar baseline characteristics. Incidence of AKI was 77 of 150 (51%) in the colistin group versus 33 of 150 (22%) in matched controls (risk difference, 29%; 95% confidence interval, 19 to 39), corresponding to a number needed to harm of 3.5. Early toxicity was apparent, because AKI risk was higher in colistin-exposed patients at 72 hours of exposure (incidence rate ratio, 1.9; 95% confidence interval, 1.1 to 3.5). In both groups, hospital mortality in patients who experienced AKI was lower if kidney function returned to baseline during hospitalization. The effect of colistin exposure on AKI risk varied inversely according to baseline hemoglobin concentration.ConclusionsColistin is associated with substantial excess AKI that is apparent within the first 72 hours of treatment. Colistin’s toxicity varied according to baseline hemoglobin concentration.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_03_15_CJASNPodcast_18_4_M.mp3