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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-01

AUTHORS

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

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. More... »

PAGES

764

Journal

TITLE

Nature Communications

ISSUE

1

VOLUME

3

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncomms1756

DOI

http://dx.doi.org/10.1038/ncomms1756

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1051043532

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22473008


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