Book Chapter

Mechanisms of Polymyxin-Induced Nephrotoxicity

Mohammad AK Azad, Roger L Nation, Tony Velkov, Jian Li

Advances in Experimental Medicine and Biology | SPRINGER INTERNATIONAL PUBLISHING AG | Published : 2019

Abstract

Polymyxin-induced nephrotoxicity is the major dose-limiting factor and can occur in up to 60% of patients after intravenous administration. This chapter reviews the latest literature on the mechanisms of polymyxin-induced nephrotoxicity and its amelioration. After filtration by glomeruli, polymyxins substantially accumulate in renal proximal tubules via receptor-mediated endocytosis mainly by megalin and PEPT2. It is believed that subsequently, a cascade of interconnected events occur, including the activation of death receptor and mitochondrial apoptotic pathways, mitochondrial damage, endoplasmic reticulum stress, oxidative stress and cell cycle arrest. The current literature shows that ox..

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University of Melbourne Researchers