Abstract

The kidney is an excretory organ having influx transporters on the basolateral membrane of proximal tubular cells and efflux transporters on the apical membrane. Cross-species changes in kidney transporter expression, function, location, and homology are crucial factors. DIKI is caused mostly by intracellular drug accumulation or metabolites and is accompanied with kidney histological abnormalities and a rise in serum creatinine (Scr). It is critical to determine whether a rise in Scr is caused by DIKI or by indirect transporter inhibition, which results in reversible and transitory drug-induced Scr increase [DICI] without histopathological abnormalities. Finally, in vitro and in vivo animal models can anticipate unexpected changes in systemic exposure and the effect of kidney transporters.

Keywords: Kidney transporters; Medication discovery; Medication development; Drug-drug interactions