How is tenofovir excreted by the kidneys

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How is tenofovir excreted by the kidneys, and how is it related to the drug’s nephrotoxicity?

TDF causes AKI and Fanconi syndrome. TDF damages the proximal tubule. It enters the proximal tubular cells via the basolateral circulation and is then transported into the intracellular space via the human organic anion transporter (OAT). It is subsequently secreted into the urinary space via efflux transporters such as multidrug-resistant protein-2 (MRP-2). Endogenous substances and drugs compete for the MRP-2 efflux transporter, impairing TDF excretion and leading to higher intracellular concentrations. A single nucleotide polymorphism of the MRP-2 gene (loss-of-function mutation) increases the risk for Fanconi syndrome. Mitochondrial injury is the major cause of the proximal tubulopathy associated with high intracellular TDF concentrations.

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