2109. Liposomal Amphotericin B-associated Nephrotoxicity in Obese and Non-obese Patients

Abstract

BackgroundLiposomal amphotericin B (L-amb) is an important antifungal agent which exhibits significant rates of dose-dependent nephrotoxicity. Animal studies demonstrate only small amounts of L-amb distribute into adipose tissue and obese animals show greater risk of nephrotoxicity with L-amb administration. This study aims to determine whether obese patients are at a higher risk of nephrotoxicity with weight-based doses of L-amb.MethodsWe performed a multi-center, retrospective cohort study of nephrotoxicity with L-amb in obese (BMI > 30) and non-obese adult patients at University of Utah Health and Intermountain Healthcare from January 1, 2014 through December 31, 2018. Our primary outcome was the rate of nephrotoxicity as determined by AKIN criteria. Patients receiving at least one dose of L-amb were identified for inclusion. Patients were excluded if they were already on a renal replacement at the time of L-amb initiation or they received L-amb prior to admission.ResultsWe included 221 patients, 47 (21%) were obese and 174 (79%) were non-obese. Median total body weight was 109 kg in obese patients compared with 70 kg in non-obese patients. Dosage based on ideal body weight was higher in the obese group (median 6.9 mg/kg vs. 4.9 mg/kg). Obese patients were significantly more likely to experience acute kidney injury (AKI) than non-obese patients (55% vs. 37%, P = 0.03). Patients who experienced nephrotoxicity received a higher average daily dose than those who did not (365 mg vs. 333 mg, P = 0.03), had a higher median cumulative dose (3,130 mg vs. 1,700 mg, P < 0.001), and had a higher median total body weight (79.6 kg vs. 71.9 kg, P = 0.04.). Additionally, daily dose normalized to total body weight was not associated with AKI (median 4.7 mg/kg in patients with AKI vs. 4.8 mg/kg in patients without AKI, P = 0.86). However, daily dose normalized to ideal body weight was associated with AKI (median 5.5 mg/kg in patients with AKI vs. 4.9 mg/kg in patients without AKI, P = 0.02).ConclusionWe identified a higher rate of nephrotoxicity among obese patients receiving L-amb compared with non-obese patients. These data suggest that dosing L-amb based on total body weight places obese patients at a higher risk of nephrotoxicity. This should be considered when assessing the risks and benefits of this dosing strategy in obese patients.Disclosures All authors: No reported disclosures.