Renal drug transporters (RDTs)

Renal drug transporters are a specialized group of membrane proteins located in the renal proximal tubule that mediate the active secretion and reabsorption of drugs and endogenous metabolites (Giacomini et al., 2010, Nature Reviews Drug Discovery). These transporters are primarily classified into the Solute Carrier (SLC) family, such as Organic Anion Transporters (OAT1, OAT3) and Organic Cation Transporters (OCT2), and the ATP-Binding Cassette (ABC) family, including P-glycoprotein (P-gp) and Multidrug Resistance-associated Proteins (MRPs) (Yin and Wang, 2016, Acta Pharmaceutica Sinica B). They play a pivotal role in determining the renal clearance and systemic exposure of a wide variety of therapeutic agents, including antibiotics, antivirals, and chemotherapeutics. Nephrotoxicity-related pharmacokinetic interactions occur when a drug inhibits or competes for these transporters, leading to the toxic accumulation of a substrate drug within the tubular cells or elevated plasma concentrations (FDA, 2020, In Vitro Drug Interaction Studies Guidance). For instance, the inhibition of MATE1/2-K transporters can reduce metformin clearance, while OAT1/3 inhibition can exacerbate methotrexate-induced kidney injury. Consequently, evaluating the interaction of new molecular entities with these transporters is a critical safety requirement in drug development to prevent drug-induced kidney injury (DIKI) and manage complex polypharmacy regimens.

Other names

Kidney transportersRenal solute carriersRenal efflux transportersNephrotoxicity-associated transportersRenal drug-drug interaction sites

Facilitation of active secretion and reabsorption of drugs across the renal proximal tubule cell membranes, often serving as a site for competitive or non-competitive inhibition leading to altered pharmacokinetics.