Recent developments in our understanding of the renal basis of hyperuricemia and the development of novel antihyperuricemic therapeutics 英文参考文献.docVIP

Available online /content/8/S1/S4 Review Recent developments in our understanding of the renal basis of hyperuricemia and the development of novel antihyperuricemic therapeutics Robert Terkeltaub1, David A Bushinsky2 and Michael A Becker3 1San Diego VAMC Rheumatology Section, and University of California San Diego, La Jolla, California, USA 2University of Rochester School of Medicine, and Nephrology Division, Strong Memorial Hospital, Rochester, New York, USA 3University of Chicago Pritzker School of Medicine, Chicago, Illinois, USA Corresponding author: Robert Terkeltaub, rterkeltaub@ Published: 12 April 2006 This article is online at /content/8/S1/S4 ? 2006 BioMed Central Ltd Arthritis Research Therapy 2006, 8(Suppl 1):S4 (doi:10.1186/ar1909) Abstract individuals [3], impaired renal excretion of uric acid is the dominant cause of hyperuricemia in the majority of patients with gout [1-3]. 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 Urate physiology highlight exciting and clinically pertinent advances in our A weak organic acid with a pKa1 of 5.75, uric acid is the final product of human purine metabolism. At the physiologic pH of 7.4 in extracellular fluid, the concentration of urate ion is approximately 50-fold that of the less soluble un-ionized uric acid. Because of the high concentration of sodium in extracellular fluid, urate is largely present as MSU; a consequence of this is that the appreciable solubility of urate ion (120 mg/dl at 37°C) is replaced by the much lower solubility of MSU (approximately 6.8 mg/dl). As urate concen- trations increasingly exceed 6.8 mg/dl, the risk for urate crystal format