Renal tubular urate transporters

Renal tubular urate transporters are a complex system of membrane proteins located in the proximal tubule of the kidney that maintain systemic uric acid homeostasis through a balance of reabsorption and secretion [1.3.1, 1.5.3]. This "urate transportasome" primarily consists of reabsorptive transporters, such as Urate Transporter 1 (URAT1/SLC22A12) and Glucose Transporter 9 (GLUT9/SLC2A9), and secretory transporters, including ABCG2 and various Organic Anion Transporters (OAT1, OAT3) [1.5.1, 1.5.2]. In humans, the majority of filtered urate is reabsorbed into the bloodstream, and genetic or acquired dysfunction in these transporters often leads to hyperuricemia, the underlying cause of gout and a risk factor for cardiovascular and renal diseases [1.1.3, 1.4.1]. Therapeutic intervention focuses on inhibiting reabsorptive transporters, particularly URAT1, using uricosuric agents like lesinurad, probenecid, and benzbromarone to enhance urinary urate excretion [1.2.1, 1.2.2]. While effective at lowering serum urate levels, these drugs can increase the risk of nephrolithiasis and acute kidney injury due to high concentrations of urate in the renal tubules [1.3.1, 1.6.1]. Consequently, these transporters are critical targets for managing metabolic and inflammatory conditions associated with disordered purine metabolism [1.3.2, 1.3.4].

Other names

Urate transportasomeRenal urate transportersUric acid transportersRenal urate transport system

Inhibition of renal urate reabsorption by blocking apical transporters (e.g., URAT1, OAT4) and basolateral transporters (e.g., GLUT9), thereby increasing urinary urate excretion and lowering serum urate levels.