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Xenobiotic Transporters in the Kidney: Function and Role in Toxicity
Xenobiotic Transporters in the Kidney: Function and Role in Toxicity
- 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.
- Subjects :
- 0301 basic medicine
030232 urology & nephrology
Renal function
Biology
Bioinformatics
Xenobiotics
Nephrotoxicity
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
medicine
Humans
Renal Insufficiency, Chronic
Solute Carrier Proteins
Kidney
Drug discovery
Transporter
Acute Kidney Injury
Solute carrier family
Kidney Tubules
030104 developmental biology
medicine.anatomical_structure
chemistry
Nephrology
ATP-Binding Cassette Transporters
Xenobiotic
Function (biology)
Subjects
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