Renal organic anion transporters in drug–drug interactions and diseases
The kidney plays a vital role in maintaining systemic homeostasis. Active tubular secretion and reabsorption, which are mainly mediated by transporters, is an efficient mechanism for retaining glucose, amino acids, and other nutrients and for the clearance of endogenous waste products and xenobiotics. These substances are recognized by uptake transporters located in the basolateral and apical membranes of renal proximal tubule cells and are extracted from plasma and urine. Organic anion transporters (OATs) belong to the solute carrier (SLC) 22 superfamily and facilitate organic anions across the plasma membranes of renal proximal tubule cells. OATs are responsible for the transmembrane transport of anionic and zwitterionic organic molecules, including endogenous substances and many drugs. The alteration in OAT expression and function caused by diseases, drug–drug interactions (DDIs) or other issues can thus change the renal disposition of substrates, induce the accumulation of toxic metabolites, and lead to unexpected clinically outcome. This review summarizes the recent information regarding the expression, regulation, and substrate spectrum of OATs and discusses the roles of OATs in diseases and DDIs. These findings will enables us to have a better understanding of the related disease therapy and the potential risk of DDIs mediated by OATs.