Renal transporters of tenofovir (OAT1, OAT3, MRP4, MRP2)

The renal transporters affecting tenofovir are a group of membrane proteins located in the proximal tubule cells of the kidney that mediate the active secretion of tenofovir from the blood into the urine. This system primarily includes the basolateral uptake transporters Organic anion transporter 1 (OAT1/SLC22A6) and Organic anion transporter 3 (OAT3/SLC22A8), which move tenofovir from the peritubular capillaries into the tubule cells, and the apical efflux transporters Multidrug resistance-associated protein 4 (MRP4/ABCC4) and Multidrug resistance-associated protein 2 (MRP2/ABCC2), which pump the drug into the tubular lumen (Ray et al., 2006; Kohler et al., 2011). These transporters are critical for the renal clearance of tenofovir, but their activity also leads to the accumulation of the drug within proximal tubule cells, which can cause mitochondrial toxicity and subsequent nephrotoxicity (Fernandez-Fernandez et al., 2011). Clinical manifestations of this toxicity include Fanconi syndrome, characterized by proteinuria, glycosuria, and phosphaturia, as well as acute or chronic declines in renal function (Mallon et al., 2014). Many drugs, such as ritonavir-boosted protease inhibitors or non-steroidal anti-inflammatory drugs (NSAIDs), can interact with these transporters, potentially increasing tenofovir concentrations and the risk of kidney injury (Uwai et al., 2007). Understanding these transporters is essential for managing patients on tenofovir-based antiretroviral therapy and for the development of safer prodrugs like tenofovir alafenamide (TAF), which has lower renal exposure.

Other names

Tenofovir renal transportersRenal proximal tubule transporters for tenofovirOAT1/3 and MRP4/2 systemRenal tenofovir transport system

Substrate for active tubular secretion; competitive inhibition of uptake (OAT1/3) or efflux (MRP4/2) transporters.