Abstract

ADVANCED SCREENING METHODS FOR TESTING NEPHROTOXICITY

Rani K. Cherian*, Sumi James, Sherly Eapen and Dr. Santhosh M. Mathews

ABSTRACT

Drug induced nephrotoxicity is a common adverse event that increases morbidity, increases healthcare use, and can impede the development of novel medications. To prevent drug-induced kidney impairment, new techniques for early and more precise identification are urgently needed. Due to different definitions of kidney injury, insufficient assessments of related risk variables, and a lack of long-term outcome reporting, our understanding of drug-induced kidney disease is currently restricted. Current in vitro 2D cell models do not accurately duplicate the morphology and intact renal tubule function, and as a result, they do not faithfully replicate in vivo nephrotoxicity. The functional proteins expressed by renal tubules that mediate drug sensitivity are well recognised. A filter unit and a tubular portion of the kidney, which together contain more than 20 different cell types, make up this delicate and complicated organ. The highly polarised nature of the tubular epithelium makes it crucial to maintain cellular polarity for optimal performance and response to environmental cues. Cellular communication, including paracrine and autocrine signals, as well as biomechanical and chemotactic mechanisms, are all necessary for maintaining cell polarity. The proliferation, migration, and differentiation of kidney cells are impacted by these mechanisms. The microenvironment is crucial for anticipating hazardous effects in drug disposal research. Considering Adverse Outcome Pathways (AOP), we discuss new technologies and models in this review that may be used to identify biomarkers and pathways involved in nephrotoxicity, including cell culture, Omic approaches, Bioinformatics platforms, CRISPR/Cas9 genome-editing, In Silico, Organoids, and 3D Bioprinting.

Keywords: Drug induced nephrotoxicity, Nephrotoxicity models, Biomarkers, Zebrafish model, Kidney on Chips, Stem cells.