Renal transport of uric acid and how this can contribute to hyperuricemia and gout
Renal urate transport consists of glomerular filtration followed by near-complete reabsorption, subsequent secretion back into the tubule, and reabsorption in the distal proximal tubule with a net renal excretion of ∼10% of filtered urate. URAT1 is an important renal urate-anion exchanger on the apical surface of the proximal tubular epithelial cell responsible for the reabsorption of filtered urate. Inhibition of URAT1 results in enhanced uricosuria and lower serum urate levels. Drugs that inhibit URAT1 include probenecid, sulfinpyrazone, benzbromarone, metabolites of losartan, high-dose salicylates, and lesinurad (the latter, highly specific for URAT1). Conversely, URAT1 is stimulated by other drugs (lactate, nicotinate, pyrazinoate, low-dose aspirin, and possibly diuretics), resulting in decreased urate excretion and hyperuricemia. GLUT9a is the major transporter on the basolateral surface of the proximal tubular epithelial cell and facilitates the transport of urate from the tubular cell into the renal interstitium. Mutations of Glut9a result in reduced urate reabsorption, lower serum urate concentrations, and a lower risk of developing gout. Other transport proteins in the renal proximal tubular epithelial cell that regulate urate secretion include OAT1 and OAT3 on the basolateral surface while ABCG2 and MRP4 are the two major proteins on the apical surface.
