Fig. 6

Lesinurad blocks URAT1 and OAT4 to enhance fractional excretion of uric acid and reduce serum urate levels. This diagram of a nephron depicts the location of urate transporters within the proximal tubule epithelial cell, and the mechanism of action of lesinurad compared to benzbromarone and probenecid. Lesinurad inhibits urate reabsorptive importers URAT1 and OAT4, and the inhibition of OAT4 may counteract postulated OAT4-dependent diuretic-induced hyperuricemia. Benzbromarone specifically inhibits URAT1 but not OAT4. Probenecid nonspecifically inhibits URAT1, OAT4, and other OAT family members, leading to drug–drug interactions involving OAT1 and OAT3. At physiologically relevant concentrations, none of these compounds inhibits GLUT9, another transporter that is important for the renal reabsorption of urate [18–21]