Abstract
Influx and efflux kidney tubular transporters are major determinants of the disposition of xenobiotics, including pharmaceutical drugs. On the basolateral membrane of proximal tubular cells, there are influx transporters, such as organic cation transporters. On the apical membrane of proximal tubular cells, there are efflux transporters, such as multidrug and toxin extrusion proteins. The secretion process across the apical membrane into the lumen occurs via efflux transporters which plays an important role in serum creatinine (sCr) elimination in urine. The interference of a pharmaceutical drug with transporters can lead to changes in sCr with no alterations in biomarkers or light microscopic evidence indicative of renal injury. Identification of transporters that influence drug disposition, toxicity, and overall nonclinical safety assessment is important in drug discovery and development programs. This mini review describes some key aspects of kidney tubular transporters and drug-induced renal toxicities in safety risk assessment and drug development.
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