Lesinurad, used as add-on to xanthine oxidase inhibitors for gout, lowers serum urate by a mechanism different from allopurinol. It acts by inhibiting:

• A Uricase enzyme in hepatocytes, preventing conversion of uric acid to allantoin
• B ABCG2 (breast cancer resistance protein) in the intestinal mucosa, blocking urate secretion
• C GLUT9 transporter in collecting duct cells, preventing urate reabsorption in the distal nephron
• D URAT1 (urate anion transporter 1) and OAT4 in the renal proximal tubule, blocking urate reabsorption ✓

Explanation

Lesinurad is a selective urate reabsorption inhibitor that blocks URAT1 (SLC22A12) and OAT4 (SLC22A11) transporters in the proximal renal tubule. URAT1 is responsible for the majority of urate reabsorption from the tubular lumen; its inhibition significantly increases urinary urate excretion (uricosuric effect). ABCG2 is a urate efflux transporter whose loss-of-function promotes hyperuricemia; lesinurad does not act on ABCG2. Pegloticase and rasburicase are recombinant uricases. GLUT9 (SLC2A9) is another important renal urate transporter but is not lesinurad's primary target.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.