URAT1 (urate transporter 1, SLC22A12)

Class

Oral uricosuric -- URAT1 inhibitor

Pathway

Renal tubular uric acid reabsorption (hyperuricemia/gout, incl. in CKD)

URAT1 (urate transporter 1, encoded by SLC22A12) is a transport protein embedded in the membrane of cells lining the kidney's proximal tubule, the segment of the nephron responsible for reclaiming most substances filtered from blood. Its normal job is to pull uric acid back out of the urine and return it to the bloodstream, a process called reabsorption. Because humans lack the enzyme (uricase) that other mammals use to break down uric acid, blood urate levels depend heavily on how efficiently the kidney reabsorbs versus excretes it. When urate reabsorption exceeds excretion, serum urate rises (hyperuricemia), and if concentrations exceed solubility limits, needle-shaped crystals can deposit in joints and soft tissue, producing gout. Blocking URAT1 reduces reabsorption, so more uric acid is excreted in urine and blood levels fall. This uricosuric strategy is relevant across the spectrum of hyperuricemic disease, including patients whose kidney function is already reduced by chronic kidney disease (CKD), a population in which impaired urate clearance can both worsen gout and be worsened by it. URAT1 inhibition offers a mechanistically distinct alternative or complement to drugs that instead reduce urate production upstream in its synthesis pathway.