title: New developments in clinically relevant mechanisms and treatment of hyperuricemia.
abstract: The prevalence of gout has increased markedly in the United States in the past two decades, and new treatments for hyperuricemia are being developed. Recent molecular identification of urate transporter-1 (URAT1) as the central mediator of renal urate reabsorption has provided novel understanding of the pathogenesis of hyperuricemia, and the target site for current and possibly future primary uricosuric agents. Recent studies have also highlighted uricosuric effects of several drugs (losartan, atorvastatin, fenofibrate) that are prescribed for primary indications other than hyperuricemia. The niche of these agents in current management of hyperuricemia is discussed. We also review the ongoing development of recombinant uricase preparations and of novel xanthine oxidase inhibitors exemplified by febuxostat. These agents should provide novel options for patients with chronic, refractory gout and hyperuricemia, particularly in association with allopurinol hypersensitivity and renal insufficiency.
authors.affiliation: University of California, San Diego, Division of Rheumatology, Allergy, and Immunology, Center for Innovative Therapy, 9320 Campus Point Dr. Suite 225, La Jolla, CA 92037-0943, USA. s2lee@uscd.edu
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Lee
authors.forename: Robert A
authors.initials: RA
authors.lastname: Terkeltaub
mesh_terms: D000069465:Febuxostat; D006801:Humans; D033461:Hyperuricemia / Q000188:drug therapy* / Q000378:metabolism*; D011379:Prognosis; D013844:Thiazoles / Q000627:therapeutic use; D014503:Urate Oxidase / Q000378:metabolism; D014527:Uric Acid / Q000378:metabolism*; D014528:Uricosuric Agents / Q000627:therapeutic use*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D013844:Thiazoles; D014528:Uricosuric Agents; D000069465:Febuxostat; D014527:Uric Acid; D014969:Xanthine Oxidase; D014503:Urate Oxidase