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

Author

Listed:
  • Kimiyoshi Ichida

    (Tokyo University of Pharmacy and Life Sciences
    Jikei University School of Medicine)

  • 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
    Aeromedical Laboratory, Japan Air Self-Defense Force)

  • 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
    Laboratory for Statistical Analysis, Center for Genomic Medicine, Institute of Physical and Chemical Research (RIKEN))

  • 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)

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.

Suggested Citation

  • Kimiyoshi Ichida & Hirotaka Matsuo & Tappei Takada & Akiyoshi Nakayama & Keizo Murakami & Toru Shimizu & Yoshihide Yamanashi & Hiroshi Kasuga & Hiroshi Nakashima & Takahiro Nakamura & Yuzo Takada & Yu, 2012. "Decreased extra-renal urate excretion is a common cause of hyperuricemia," Nature Communications, Nature, vol. 3(1), pages 1-7, January.
    • Handle: RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms1756
    DOI: 10.1038/ncomms1756
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