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Amphotericin B-induced nephrotoxicity: characterization of blood and urinary biochemistry and renal morphology in mice

Drug Safety Evaluation, Developmental Research Laboratories, Toyonaka, Osaka, Japan

E. Yamamoto

Drug Safety Evaluation, Developmental Research Laboratories, Toyonaka, Osaka, Japan

C. Kondo

Drug Safety Evaluation, Developmental Research Laboratories, Toyonaka, Osaka, Japan

A. Itoh

Drug Safety Evaluation, Developmental Research Laboratories, Toyonaka, Osaka, Japan

N. Tsuchiya

Drug Safety Evaluation, Developmental Research Laboratories, Toyonaka, Osaka, Japan

T. Uehara

Drug Safety Evaluation, Developmental Research Laboratories, Toyonaka, Osaka, Japan, takeki.uehara{at}shionogi.co.jp

T. Baba

Drug Safety Evaluation, Developmental Research Laboratories, Toyonaka, Osaka, Japan

This study was conducted to characterize blood and urinary biochemistry, and renal morphology, after single or 1-week repeated dosing of mice with the polyene macrolide antibiotic, amphotericin B (AMB). AMB was intravenously administered to mice at 2 or 4 mg/kg for the single-dose experiment or once daily at 1 or 2 mg/kg for 1 week for the repeated-dose experiment. The most prominent histopathological findings included necrosis of the tubular epithelial cells in the thick ascending limb of Henle’s loop in the renal outer medulla at a single dose of 2 or 4 mg/kg, and the severity of the lesion was dose-dependent. Blood chemistry and urinalysis revealed several changes suggestive of renal dysfunction such as reduction of plasma filtration ability (increases in plasma creatinine and blood urea nitrogen, a decrease in creatinine clearance) and polyuria accompanied with dehydration (decrease in renal water reabsorption, increases in plasma total protein and albumin) at a dose of 4 mg/kg in the single-dose experiment. Among the parameters analyzed, urinary lactate dehydrogenase was the most sensitive and reliable parameter for the prediction of AMB-induced nephrotoxicity in mice. These data provided comprehensive information on the nephrotoxicity of AMB and indicate useful markers for the sensitive detection of AMB-induced renal injury in mice.

Key Words: amphotericin B • mice • nephrotoxicity • urinary lactate dehydrogenase

This version was published on May 1, 2009

Human & Experimental Toxicology, Vol. 28, No. 5, 293-300 (2009)
DOI: 10.1177/0960327109105404


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