{"title":"Kidney transporters drug discovery, development, and safety","authors":"Zaher A. Radi , Yurong Lai","doi":"10.1016/j.cotox.2022.02.005","DOIUrl":null,"url":null,"abstract":"<div><p><span>Kidney is an excretion organ with influx transporters on the basolateral membrane<span> of proximal tubular cells and efflux transporters on the apical membrane of proximal tubular cells. Cross-species differences in the expression, function, localization, and homology of kidney transporters are important considerations. Drug-indued </span></span>kidney injury<span><span> (DIKI) is mainly due to the intracellular drug accumulation or their metabolites and is associated with kidney histopathological changes and increase in serum creatinine (Scr). It is important to distinguish if an increase in Scr is related to DIKI or indirect inhibition of transporters leading to reversible and transient drug-induced Scr increase [DICI] without histopathological lesions. Finally, in vitro and in vivo </span>animal models can predict unexpected changes in systemic exposure and kidney transporter-mediated effect.</span></p></div>","PeriodicalId":37736,"journal":{"name":"Current Opinion in Toxicology","volume":"29 ","pages":"Pages 65-69"},"PeriodicalIF":6.1000,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Opinion in Toxicology","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2468202022000092","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"TOXICOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Kidney is an excretion organ with influx transporters on the basolateral membrane of proximal tubular cells and efflux transporters on the apical membrane of proximal tubular cells. Cross-species differences in the expression, function, localization, and homology of kidney transporters are important considerations. Drug-indued kidney injury (DIKI) is mainly due to the intracellular drug accumulation or their metabolites and is associated with kidney histopathological changes and increase in serum creatinine (Scr). It is important to distinguish if an increase in Scr is related to DIKI or indirect inhibition of transporters leading to reversible and transient drug-induced Scr increase [DICI] without histopathological lesions. Finally, in vitro and in vivo animal models can predict unexpected changes in systemic exposure and kidney transporter-mediated effect.
期刊介绍：
The aims and scope of Current Opinion in Toxicology is to systematically provide the reader with timely and provocative views and opinions of the highest qualified and recognized experts on current advances in selected topics within the field of toxicology. The goal is that Current Opinion in Toxicology will be an invaluable source of information and perspective for researchers, teachers, managers and administrators, policy makers and students. Division of the subject into sections: For this purpose, the scope of Toxicology is divided into six selected high impact themed sections, each of which is reviewed once a year: Mechanistic Toxicology, Metabolic Toxicology, Risk assessment in Toxicology, Genomic Toxicology, Systems Toxicology, Translational Toxicology.
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