The Use of Renal Cell Culture for Nephrotoxicity Investigations

The kidney is especially susceptible to toxicity induced by xenobiotics due to its role in transport, metabolism, and excretion of endogenous and exogenous compounds. The glomerulus and the proximal tubule region are the two regions most often perturbed in disease states and adversely affected by xenobiotics. In order to study these events at a cellular level, primary cell culture protocols have been developed for both proximal tubule and podocytes and a number of cell lines are also available. In addition, approaches are being developed to differentiate human inducible pluripotent stem cells into podocyte and proximal tubule lineages. In parallel, the application of omics technologies to toxicological investigations is accelerating our knowledge of how cells interact with and react to xenobiotics at molecular and cellular levels. Advances in cell culture techniques, such as the development of microfluidic devices, are further improving desired phenotypes and creating new possibilities such as multiorgan testing. These advances together are significantly advancing the field of human in vitro toxicity testing, which will likely lead to real alternatives to animal studies in preclinical investigations. Here, we give a review of the field of in vitro nephrotoxicity from physiological and cell culture perspectives.