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Decreased extra-renal urate excretion is a common cause of hyperuricemia

2012; Nature Portfolio; Volume: 3; Issue: 1 Linguagem: Inglês

10.1038/ncomms1756

2041-1723

Kimiyoshi Ichida, Hirotaka Matsuo, Tappei Takada, Akiyoshi Nakayama, Keizo Murakami, Toru Shimizu, Yoshihide Yamanashi, Hiroshi Kasuga, Hiroshi Nakashima, Takahiro Nakamura, Yuzo Takada, Yusuke Kawamura, Hiroki Inoue, Chisa Okada, Yoshitaka Utsumi, Yuki Ikebuchi, Kousei Ito, Makiko Nakamura, Yoshihiko Shinohara, Makoto Hosoyamada, Yutaka Sakurai, Nariyoshi Shinomiya, Tatsuo Hosoya, Hiroshi Suzuki,

Eosinophilic Disorders and Syndromes

ABCG2, also known as BCRP, is a high-capacity urate exporter, the dysfunction of which raises gout/hyperuricemia risk. Generally, hyperuricemia has been classified into urate 'overproduction type' and/or 'underexcretion type' based solely on renal urate excretion, without considering an extra-renal pathway. Here we show that decreased extra-renal urate excretion caused by ABCG2 dysfunction is a common mechanism of hyperuricemia. Clinical parameters, including urinary urate excretion, are examined in 644 male outpatients with hyperuricemia. Paradoxically, ABCG2 export dysfunction significantly increases urinary urate excretion and risk ratio of urate overproduction. Abcg2-knockout mice show increased serum uric acid levels and renal urate excretion, and decreased intestinal urate excretion. Together with high ABCG2 expression in extra-renal tissues, our data suggest that the 'overproduction type' in the current concept of hyperuricemia be renamed 'renal overload type', which consists of two subtypes—'extra-renal urate underexcretion' and genuine 'urate overproduction'—providing a new concept valuable for the treatment of hyperuricemia and gout. Hyperuricemia, or gout, is thought to arise either from urate overproduction or from decreased renal excretion of urate. Ichidaet al. show that the extra-renal excretion of urate also has a role in the pathogenesis of hyperuricemia, and propose a new classification for patients with this disease.