title: Xenobiotic transporters and kidney injury.
abstract: Renal proximal tubules are targets for toxicity due in part to the expression of transporters that mediate the secretion and reabsorption of xenobiotics. Alterations in transporter expression and/or function can enhance the accumulation of toxicants and sensitize the kidneys to injury. This can be observed when xenobiotic uptake by carrier proteins is increased or efflux of toxicants and their metabolites is reduced. Nephrotoxic chemicals include environmental contaminants (halogenated hydrocarbon solvents, the herbicide paraquat, the fungal toxin ochratoxin, and heavy metals) as well as pharmaceuticals (certain beta-lactam antibiotics, antiviral drugs, and chemotherapeutic drugs). This review explores the mechanisms by which transporters mediate the entry and exit of toxicants from renal tubule cells and influence the degree of kidney injury. Delineating how transport proteins regulate the renal accumulation of toxicants is critical for understanding the likelihood of nephrotoxicity resulting from competition for excretion or genetic polymorphisms that affect transporter function.
authors.affiliation: Department of Pharmacology and Toxicology, Rutgers University Ernest Mario School of Pharmacy, 170 Frelinghuysen Road, Piscataway, NJ 08854, USA.
authors.forename: Blessy
authors.initials: B
authors.lastname: George
authors.affiliation: Department of Pharmacology and Toxicology, Rutgers University Ernest Mario School of Pharmacy, 170 Frelinghuysen Road, Piscataway, NJ 08854, USA.
authors.forename: Dahea
authors.initials: D
authors.lastname: You
authors.affiliation: Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO 80045, USA; Division of Renal Diseases and Hypertension, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: Melanie S
authors.initials: MS
authors.lastname: Joy
authors.affiliation: Department of Pharmacology and Toxicology, Rutgers University Ernest Mario School of Pharmacy, 170 Frelinghuysen Road, Piscataway, NJ 08854, USA; Environmental and Occupational Health Sciences Institute, 170 Frelinghuysen Road, Piscataway, NJ 08854, USA; Rutgers Center for Lipid Research, New Jersey Institute for Food, Nutrition, and Health, Rutgers University, New Brunswick, New Jersey 08901, USA. Electronic address: aleksunes@eohsi.rutgers.edu.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Aleksunes
mesh_terms: D000818:Animals; D002352:Carrier Proteins; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D026901:Membrane Transport Proteins; D015262:Xenobiotics / Q000493:pharmacokinetics*
chemical_list: D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D015262:Xenobiotics
keywords: BCRP; MATE1; MATE2-K; MDR1; MRP2; OAT; OCT2; OCTN2; Transporters