title: Decreased extra-renal urate excretion is a common cause of hyperuricemia.
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.
authors.affiliation: Department of Pathophysiology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachiouji, Tokyo 192-0392, Japan. ichida@toyaku.ac.jp
authors.forename: Kimiyoshi
authors.initials: K
authors.lastname: Ichida
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Matsuo
authors.forename: Tappei
authors.initials: T
authors.lastname: Takada
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Nakayama
authors.forename: Keizo
authors.initials: K
authors.lastname: Murakami
authors.forename: Toru
authors.initials: T
authors.lastname: Shimizu
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Yamanashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kasuga
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakashima
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakamura
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Takada
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kawamura
authors.forename: Hiroki
authors.initials: H
authors.lastname: Inoue
authors.forename: Chisa
authors.initials: C
authors.lastname: Okada
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Utsumi
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ikebuchi
authors.forename: Kousei
authors.initials: K
authors.lastname: Ito
authors.forename: Makiko
authors.initials: M
authors.lastname: Nakamura
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Shinohara
authors.forename: Makoto
authors.initials: M
authors.lastname: Hosoyamada
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Sakurai
authors.forename: Nariyoshi
authors.initials: N
authors.lastname: Shinomiya
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Hosoya
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D000818:Animals; D001692:Biological Transport; D015536:Down-Regulation; D006801:Humans; D033461:Hyperuricemia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D014527:Uric Acid / Q000378:metabolism*
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; C501412:Abcg2 protein, mouse; D009363:Neoplasm Proteins; D014527:Uric Acid