Discovery Toxicology Approaches to Assessment of Drug-Induced Kidney Injury (S01-5)

Although advancements in recent years have led to qualification of nonclinical and clinical peripheral biomarkers of kidney injury with greater sensitivity than traditional clinical pathology endpoints, further work needs to be undertaken to better define appropriate uses and limitations of these biomarkers in early drug discovery programs. In addition, recent advances in developing novel renal in vitro models (microphysiological systems, complex in vitro models) for prediction of in vivo/clinical DIKI have started yielding promising results. In this presentation, we will discuss integration of in silico, in vitro, and exploratory in vivo studies, and kidney injury biomarkers as a comprehensive strategy for prevention/mitigation of DIKI in early discovery toxicology programs. Emphasis will be on discussing potential options for assessing and characterizing renal toxicity in various stages of the drug discovery paradigm – from target identification, through lead optimization, and up to candidate nomination. Practical examples of how this strategy has been applied to discovery programs will be further discussed. In addition, potential benefits, challenges, and opportunities of using kidney injury biomarkers and in vitro models in the current regulatory landscape will be highlighted and discussed.