Recent developments in our understanding of the renal basis of hyperuricemia and the development of novel antihyperuricemic therapeutics.
Although dietary, genetic, or disease-related excesses in urate production may contribute to hyperuricemia, impaired renal excretion of uric acid is the dominant cause of hyperuricemia in the majority of patients with gout. The aims of this review are to highlight exciting and clinically pertinent advances in our understanding of how uric acid is reabsorbed by the kidney under the regulation of urate transporter (URAT)1 and other recently identified urate transporters; to discuss urate-lowering agents in clinical development; and to summarize the limitations of currently available antihyperuricemic drugs. The use of uricosuric drugs to treat hyperuricemia in patients with gout is limited by prior urolothiasis or renal dysfunction. For this reason, our discussion focuses on the development of the novel xanthine oxidase inhibitor febuxostat and modified recombinant uricase preparations.
Terkeltaub
Robert
R
San Diego VAMC Rheumatology Section, and University of California San Diego, La Jolla, California, USA. rterkeltaub@ucsd.edu
Bushinsky
David A
DA
Becker
Michael A
MA
D002352:Carrier Proteins / Q000378:metabolism; D004032:Diet; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D033461:Hyperuricemia / Q000188:drug therapy* / Q000503:physiopathology*; D007668:Kidney / Q000503:physiopathology*; D027361:Organic Anion Transporters / Q000378:metabolism; D027701:Organic Cation Transport Proteins; D014503:Urate Oxidase / Q000378:metabolism; D014527:Uric Acid / Q000378:metabolism / Q000652:urine; D014528:Uricosuric Agents / Q000627:therapeutic use; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism
D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; C491241:SLC22A12 protein, human; D014528:Uricosuric Agents; D014527:Uric Acid; D014969:Xanthine Oxidase; D014503:Urate Oxidase