Kidney microphysiological models for nephrotoxicity assessment

Abstract

Nephrotoxicity testing is an important step in preclinical development of new molecular entities (NMEs) and has traditionally been performed in 2D cell culture systems and animal models. However, 2D culture systems fail to replicate complex in vivo microenvironment and animal models face interspecies differences including the overexpression of drug transporters. In the last decade, 3D microphysiological systems (MPS) have been developed to address these concerns. Here, we review recent advancements in kidney MPS and their application in drug-induced toxicity testing and kidney disease research. We find that current research is making significant progress addressing MPS limitations such as throughput, incorporating various regions of the nephron such as the glomerulus, and successfully modeling and predicting clinically relevant nephrotoxicity of current and new drugs.