SLC5 Sodium-Anion Cotransporters and Renal Urate Transport.

Renal urate transport plays a key role in determining the concentration of circulating uric acid. The reabsorption of filtered urate by the renal proximal tubule appears to require apical sodium-dependent anion transport and the apical URAT1 urate-anion exchanger, in that sodium-dependent transport of lactate, ketoacids, nicotinate, and pyrazinoate (PZA) increases the intracellular concentration of substrates for the subsequent exchange with luminal urate. We have identified SLC5A8 and SLC5A12 as candidates for the sodium-anion cotransporter that collaborates with URAT1. Both transporters function as sodium-dependent nicotinate/monocarboxylate/PZA transporters. Localization studies reveal serial co-expression of these transporters with URAT1, with Slc5a12 in the early proximal tubule and Slc5a8 in S2 and S3 segments. Renal urate excretion is conceivably affected by changes in the activity of SLC5A8, SLC5A12, and/or URAT1, with implications for the pathogenesis of hyperuricemia, nephrolithiasis, and related disorders. © 2007 American Institute of Physics [ABSTRACT FROM AUTHOR]