TY - JOUR T1 - Emerging Kidney Models to Investigate Metabolism, Transport and Toxicity of Drugs and Xenobiotics JF - Drug Metabolism and Disposition JO - Drug Metab Dispos DO - 10.1124/dmd.118.082958 SP - dmd.118.082958 AU - Piyush Bajaj AU - Swapan K Chowdhury AU - Robert Yucha AU - Edward J Kelly AU - Guangquing Xiao Y1 - 2018/01/01 UR - http://dmd.aspetjournals.org/content/early/2018/08/03/dmd.118.082958.abstract N2 - Kidney is a major clearance organ of the body responsible for the elimination of many xenobiotics and prescription drugs. With its multitude of uptake and efflux transporters, and metabolizing enzymes, the proximal tubule cell (PTC) in the nephron plays a key role in the disposition of these molecules and is also a primary site for toxicity. In this mini-review, we first provide an overview of the major transporters and metabolizing enzymes in the PTCs responsible for biotransformation and disposition of drugs. Next, we discuss the different cell sources that have been used to model the PTCs in vitro, their pros and cons, and their characterization. As current technology is inadequate to reliably evaluate drug disposition and toxicity in the kidney, the review then discusses recent advancements in kidney microphysiological systems (MPS) and the need to develop robust in vitro platforms that could be routinely used by pharmaceutical companies to screen compounds. Finally, we discuss the new and exciting field of stem cell derived kidney models as potential cell sources for future kidney MPS. Given the push from both regulatory agencies and pharma companies to use more predictive "human-like" in vitro systems in the early stages of drug development to reduce attrition, these emerging models have the potential to be a game changer and may revolutionize how renal disposition and kidney toxicity in drug discovery is evaluated in the future. ER -