Urinary excretion accounts for two-thirds of total elimination of uric acid and the remainder is excreted in faeces.
Urate is not protein bound and is freely filtered at the
glomerulus, but up to 90% of filtered urate is reabsorbed
(Figure 1). The main transporters responsible for tubular
reabsorption are SLC22A12 (UR AT1 - dominant expression is in the kidney and apical in tubular cells) and
SLC2A9 (GLU T9 – widely expressed, but most likely
basolateral in tubular cells), while SLC22A11 (OAT4 - apical) is less important and the evidence is weaker [5].
There also seems to be tubular secretion of urate with
some evidence existing for AB CG2, SLC17A1, SLC17A3
(apical) and SLC22A6 (OAT1) and SLC22A8 (OAT3)
(both basolateral) [5]. Probenecid, benzbromarone and
lesinurad all inhibit UR AT1, thereby reducing serum urate
levels. Non-renal elimination of urate is poorly understood: a recent publication suggests that uric acid is also
secreted directly into the intestinal lumen, but not via the
bile [6]; studies in Caco2 cells indicate that ABCG2 is important for this route of urate elimination