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Xenobiotic Transporters in the Kidney: Function and Role in Toxicity

Xenobiotic Transporters in the Kidney: Function and Role in Toxicity

Authors :
Lois D. Lehman-McKeeman
Hong Shen
Renato J. Scialis
Source :
Seminars in Nephrology. 39:159-175
Publication Year :
2019
Publisher :
Elsevier BV, 2019.

Abstract

The kidney plays a critical role in the elimination of many xenobiotics, and drug-induced kidney injury is a risk factor in drug discovery and development. In addition, accumulation of nephrotoxic compounds, a process often controlled by xenobiotic transporters, is often a prerequisite to kidney injury. Such adverse events are dependent on many transporters, particularly those in the solute carrier and adenosine triphosphate-binding cassette superfamilies. This review details the current understanding of how kidney transporters contribute to toxic outcomes and highlights critical knowledge gaps regarding species differences that account for some lack of predictivity between preclinical animal models and human beings. The basic classification, physiological roles, and species differences of solute carrier and adenosine triphosphate-binding cassette transporters is reviewed, along with mechanistic details for drug-induced kidney injury involving transporters. The use of preclinical data (in vitro and in vivo), clinical data, and conventional as well as emerging tools for studying kidney transporter function are summarized. Finally, we highlight some challenges and opportunities to improve experimental approaches to support preclinical and clinical studies of kidney transporters and their role in nephrotoxicity.

Details

ISSN :
02709295
Volume :
39
Database :
OpenAIRE
Journal :
Seminars in Nephrology
Accession number :
edsair.doi.dedup.....bd2b9ef02bab4eaa3971caf0485c9219
Full Text :
https://doi.org/10.1016/j.semnephrol.2018.12.010