Molecular identification of a renal urate–anion exchanger that regulates blood urate levels

Atsushi Enomoto, Hiroaki Kimura, Arthit Chairoungdua, Yasuhiro Shigeta, Promsuk Jutabha, Seok Ho Cha, Makoto Hosoyamada, Michio Takeda, Takashi Sekine, Takashi Igarashi, Hirotaka Matsuo, Yuichi Kikuchi, Takashi Oda, Kimiyoshi Ichida, Tatsuo Hosoya, Kaoru Shimokata, Toshimitsu Niwa, Yoshikatsu Kanai and Hitoshi Endou ()
Additional contact information
Atsushi Enomoto: Kyorin University School of Medicine
Hiroaki Kimura: Kyorin University School of Medicine
Arthit Chairoungdua: Kyorin University School of Medicine
Yasuhiro Shigeta: Kyorin University School of Medicine
Promsuk Jutabha: Kyorin University School of Medicine
Seok Ho Cha: Kyorin University School of Medicine
Makoto Hosoyamada: Kyorin University School of Medicine
Michio Takeda: Kyorin University School of Medicine
Takashi Sekine: The University of Tokyo
Takashi Igarashi: The University of Tokyo
Hirotaka Matsuo: Kyorin University School of Medicine
Yuichi Kikuchi: National Defense Medical College
Takashi Oda: JSDF Kumamoto Hospital
Kimiyoshi Ichida: The Jikei University School of Medicine
Tatsuo Hosoya: The Jikei University School of Medicine
Kaoru Shimokata: Nagoya University School of Medicine
Toshimitsu Niwa: Nagoya University School of Medicine
Yoshikatsu Kanai: Kyorin University School of Medicine
Hitoshi Endou: Kyorin University School of Medicine

Nature, 2002, vol. 417, issue 6887, 447-452

Abstract: Abstract Urate, a naturally occurring product of purine metabolism, is a scavenger of biological oxidants implicated in numerous disease processes1,2,3, as demonstrated by its capacity of neuroprotection4,5. It is present at higher levels in human blood (200–500 µM) than in other mammals6, because humans have an effective renal urate reabsorption system, despite their evolutionary loss of hepatic uricase by mutational silencing6,7,8. The molecular basis for urate handling in the human kidney remains unclear because of difficulties in understanding diverse urate transport systems and species differences6,9,10. Here we identify the long-hypothesized9,10,11 urate transporter in the human kidney (URAT1, encoded by SLC22A12), a urate–anion exchanger regulating blood urate levels and targeted by uricosuric and antiuricosuric agents (which affect excretion of uric acid). Moreover, we provide evidence that patients with idiopathic renal hypouricaemia (lack of blood uric acid) have defects in SLC22A12. Identification of URAT1 should provide insights into the nature of urate homeostasis, as well as lead to the development of better agents against hyperuricaemia, a disadvantage concomitant with human evolution.

Date: 2002
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DOI: 10.1038/nature742

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