Molecular Pathophysiology of Uric Acid Homeostasis

Uric acid, the end product of purine metabolism, plays a key role in the pathogenesis of gout and other disease processes. The circulating serum uric acid concentration is governed by the relative balance of hepatic production, intestinal secretion, and renal tubular reabsorption and secretion. An elegant synergy between genome-wide association studies and transport physiology has led to the identification and characterization of the major transporters involved with urate reabsorption and secretion, in both kidney and intestine. This development, combined with continued analysis of population-level genetic data, has yielded an increasingly refined mechanistic understanding of uric acid homeostasis as well as greater understanding of the genetic and acquired influences on serum uric acid concentration. The continued delineation of novel and established regulatory pathways that regulate uric acid homeostasis promises to lead to a more complete understanding of uric acid-associated diseases and to identify new targets for treatment.