Risk factors for acute kidney injury (AKI) in patients treated with polymyxin B and influence of AKI on mortality: A multicentre prospective cohort study

Abstract

Objectives: The objectives of this study were to assess risk factors for acute kidney injury (AKI) in patients treated with polymyxin B, a last resort antibiotic against Gram-negative bacteria, with a focus on dose, and to determine the impact of AKI on mortality of these patients. Methods: A multicentre prospective cohort study was performed including patients≥18 years treated with intravenous polymyxin B for ≥48 h. The primary outcome was AKI defined by RIFLE criteria. Secondary outcomeswere 30 day mortality and failure stage of AKI. Multivariate analysis with a Cox regression model was performed. The probability of developing AKI was determined in a logistic regression model. Results: Four-hundred-and-ten patients were included. AKI occurred in 189 (46.1%) patients. Polymyxin B dose ≥150 mg/day was a risk factor for AKI: adjusted HR=1.95, 95% CI=1.31-2.89, P=0.01. Higher weight and age were also independently associated with AKI. The probability of developing AKI significantly increased with doses between 150 and 199 mg/day, regardless of patient weight, with no significant increase with higher doses. Higher weight also increased the risk in patients receiving the same daily doses. AKI was barely associated with increased risk for 30 day mortality (adjusted HR=1.35, 95% CI=0.99-1.85, P=0.06), while ≥150 mg/day did not increase this risk despite its association with AKI. Conclusions: Polymyxin B total dose is highly related to the risk of AKI, regardless of patient weight. Thirty-daymortality tended to be higher in patientswho developed AKI. The relationship between dose, AKI andmortalitymust be further investigated in studies specifically designed to evaluate this latter outcome.