HUMAN RENAL ORGANIC ANION TRANSPORTER 1 (hOAT1) AND ITS ROLE IN THE NEPHROTOXICITY OF ANTIVIRAL NUCLEOTIDE ANALOGS

Abstract

hOAT1 is a renal membrane protein able to efficiently transport acyclic nucleoside phosphonates (ANPs). When expressed in CHO cells, hOAT1 mediates the uptake and cytotoxicity of ANPs suggesting that it plays an active role in the nephrotoxicity associated with cidofovir CMV therapy and high-dose adefovir HIV therapy. Although efficiently transported by hOAT1, tenofovir did not show any significant cytotoxicity in isolated human proximal tubular cells, which correlates with the lack of nephrotoxicity observed in HIV-infected patients on prolonged tenofovir therapy.

ACKNOWLEDGMENTS

We would like to thank Dr. Kenneth McMartin and Dona Ross from Louisiana State University at Shreveport for providing us with primary isolates of RPTECs and for excellent technical assistance with their culturing.