Renal Transport of Uric Acid: Evolving Concepts and Uncertainties

In addition to its role as a metabolic waste product, uric acid has been proposed to be an important molecule with multiple functions in human physiologic and pathophysiologic processes and may be linked to human diseases beyond nephrolithiasis and gout. Uric acid homeostasis is determined by the balance between production, intestinal secretion, and renal excretion. The kidney is an important regulator of circulating uric acid levels by reabsorbing about 90% of filtered urate and being responsible for 60% to 70% of total body uric acid excretion. Defective renal handling of urate is a frequent pathophysiologic factor underpinning hyperuricemia and gout. Despite tremendous advances over the past decade, the molecular mechanisms of renal urate transport are still incompletely understood. Many transport proteins are candidate participants in urate handling, with URAT1 and GLUT9 being the best characterized to date. Understanding these transporters is increasingly important for the practicing clinician as new research unveils their physiologic characteristics, importance in drug action, and genetic association with uric acid levels in human populations. The future may see the introduction of new drugs that act specifically on individual renal urate transporters for the treatment of hyperuricemia and gout.