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

ABSTRACT: BACKGROUND AND OBJECTIVES:Despite 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, & MEASUREMENTS:We 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. RESULTS:The 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. CONCLUSIONS:Colistin 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. PODCAST:This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_03_15_CJASNPodcast_18_4_M.mp3.

SUBMITTER: Miano TA

PROVIDER: S-EPMC5969457 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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

Miano Todd A TA Lautenbach Ebbing E Wilson F Perry FP Guo Wensheng W Borovskiy Yuliya Y Hennessy Sean S

Clinical journal of the American Society of Nephrology : CJASN 20180315 4

<h4>Background and objectives</h4>Despite 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.<h4>Design, setting, participants, & measurements</ ...[more]

PMID: 29545383

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Project description:BackgroundCase reports indicate that the use of fluoroquinolones may lead to acute kidney injury. We studied the association between the use of oral fluoroquinolones and acute kidney injury, and we examined interaction with renin-angiotensin-system blockers.MethodsWe formed a nested cohort of men aged 40-85 enrolled in the United States IMS LifeLink Health Plan Claims Database between 2001 and 2011. We defined cases as men admitted to hospital for acute kidney injury, and controls were admitted to hospital with a different presenting diagnosis. Using risk-set sampling, we matched 10 controls to each case based on hospital admission, calendar time (within 6 wk), cohort entrance (within 6 wk) and age (within 5 yr). We used conditional logistic regression to assess the rate ratio (RR) for acute kidney injury with current, recent and past use of fluoroquinolones, adjusted by potential confounding variables. We repeated this analysis with amoxicillin and azithromycin as controls. We used a case-time-control design for our secondary analysis.ResultsWe identified 1292 cases and 12 651 matched controls. Current fluoroquinolone use had a 2.18-fold (95% confidence interval [CI] 1.74-2.73) higher adjusted RR of acute kidney injury compared with no use. There was no association between acute kidney injury and recent (adjusted RR 0.87, 95% CI 0.66-1.16) or past (RR 0.86, 95% CI 0.66-1.12) use. The absolute increase in acute kidney injury was 6.5 events per 10 000 person-years. We observed 1 additional case per 1529 patients given fluoroquinolones or per 3287 prescriptions dispensed. The dual use of fluoroquinolones and renin-angiotensin-system blockers had an RR of 4.46 (95% CI 2.84-6.99) for acute kidney injury. Our case-time-control analysis confirmed an increased risk of acute kidney injury with fluoroquinolone use (RR 2.16, 95% CI 1.52-3.18). The use of amoxicillin or azithromycin was not associated with acute kidney injury.InterpretationWe found a small, but significant, increased risk of acute kidney injury among men with the use of oral fluoroquinolones, as well as a significant interaction between the concomitant use of fluoroquinolones and renin-angiotensin-system blockers.

Dataset Information

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

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

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