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

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 and Hiroshi Suzuki
Additional contact information
Kimiyoshi Ichida: Tokyo University of Pharmacy and Life Sciences
Hirotaka Matsuo: National Defense Medical College
Tappei Takada: The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo
Akiyoshi Nakayama: National Defense Medical College
Keizo Murakami: The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo
Toru Shimizu: Midorigaoka Hospital
Yoshihide Yamanashi: The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo
Hiroshi Kasuga: The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo
Hiroshi Nakashima: National Defense Medical College
Takahiro Nakamura: Laboratory for Mathematics, Premedical Course, National Defense Medical College
Yuzo Takada: Laboratory for Biofunctions, The Central Research Institute, National Defense Medical College
Yusuke Kawamura: National Defense Medical College
Hiroki Inoue: National Defense Medical College
Chisa Okada: National Defense Medical College
Yoshitaka Utsumi: National Defense Medical College
Yuki Ikebuchi: The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo
Kousei Ito: The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo
Makiko Nakamura: Tokyo University of Pharmacy and Life Sciences
Yoshihiko Shinohara: Tokyo University of Pharmacy and Life Sciences
Makoto Hosoyamada: Teikyo University School of Pharmaceutical Sciences
Yutaka Sakurai: National Defense Medical College
Nariyoshi Shinomiya: National Defense Medical College
Tatsuo Hosoya: Jikei University School of Medicine
Hiroshi Suzuki: The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo

Nature Communications, 2012, vol. 3, issue 1, 1-7

Abstract: Abstract 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.

Date: 2012
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms1756

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DOI: 10.1038/ncomms1756

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