Cellular and Molecular Mechanisms of Kidney Toxicity

Abstract

Toxicant-induced acute kidney injury is responsible for millions of deaths each year. An underlying cause of toxicant-induced acute kidney injury is renal cell death. As such, understanding the mechanisms by which toxicants cause renal cell death can aid the development of targeted therapies for the prevention and treatment of kidney disease. Accordingly, this article focuses on cellular and molecular mechanisms of nephrotoxicity. This article describes specific factors that make the kidney vulnerable to toxicants. Selective transporters and enzymes that are involved in toxicant uptake and metabolism in kidney cells, respectively, are highlighted. The role of reactive oxygen species in nephrotoxicity is discussed, followed by a review of the types of cell death pathways induced in renal cells after toxicant exposure, with a particular emphasis on the role of signaling pathways. Roles for the mitochondria, endoplasmic reticulum, and nucleus in renal cell death signaling pathways are discussed, and current challenges in the field are reviewed.

Keywords: Kidney; acute kidney injury; drug-induced kidney injury; nephrotoxicity; renal cell death.