Renal urate handling: clinical relevance of recent advances

Urate is the major inert end product of purine degradation in higher primates in contrast to most other mammals because of the genetic silencing of hepatic oxidative enzyme uricase. The kidney plays a dominant role in urate elimination. The kidney excretes 70% of the daily urate production. Therefore, it is important to understand renal urate handling mechanism because the under excretion of urate has been implicated in the development of hyperuricemia that leads to gout. The urate transport systems exist in the proximal tubule but they are complicated because of their bidirectional transport and the species differences. Recently, we have identified the urate-anion exchanger URAT1 (SLC22A12) in the human kidney and found that defects in SLC22A12 lead to idiopathic renal hypouricemia. URAT1 is targeted by uricosuric and antiuricosuric agents that affect urate excretion. Molecular identification of urate transporting proteins will lead to the new drug development for hyperuricemia.