title: Time to target uric acid to retard CKD progression.
abstract: Uric acid (UA) remains a possible risk factor of chronic kidney disease (CKD) but its potential role should be elucidated given a fact that multidisciplinary treatments assure a sole strategy to inhibit the progression to end-stage renal disease (ESRD). In clinical setting, most observational studies showed that elevation of serum uric acid (SUA) independently predicts the incidence and the development of CKD. The meta-analysis showed that SUA-lowering therapy with allopurinol may retard the progression of CKD but did not reach conclusive results due to small-sized studies. Larger scale, randomized placebo-controlled trials to assess SUA-lowering therapy are needed. Our recent analysis by propensity score methods has shown that the threshold of SUA should be less than 6.5 mg/dL to abrogate ESRD. In animal models an increase in SUA by the administration of oxonic acid, uricase inhibitor, or nephrectomy can induce glomerular hypertension, arteriolosclerosis including afferent arteriolopathy and tubulointerstitial fibrosis. The ever-growing discoveries of urate transporters prompt us to learn UA metabolism in the kidney and intestine. One example is that the intestinal ABCG2 may play a compensatory role at face of decreased renal clearance of UA in nephrectomized rats, the trigger of which is not a uremic toxin but SUA itself. This review will summarize the recent knowledge on the relationship between SUA and the kidney and try to draw a conclusion when and how to treat asymptomatic hyperuricemia accompanied by CKD. Finally we will address a future perspective on UA study including a Mendelian randomization approach.
authors.affiliation: Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan.|Support for Community Medicine Endowed Chair, Teikyo University School of Medicine, Tokyo, 173-8605, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Kumagai
authors.affiliation: Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan.
authors.forename: Tatsuru
authors.initials: T
authors.lastname: Ota
authors.affiliation: Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan.
authors.forename: Yoshifuru
authors.initials: Y
authors.lastname: Tamura
authors.affiliation: Department of Nephrology, Tianjin First Central Hospital, Tianjin, China.
authors.forename: Wen Xiu
authors.initials: WX
authors.lastname: Chang
authors.affiliation: Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Shibata
authors.affiliation: Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan. s_uchida@netjoy.ne.jp.
authors.forename: Shunya
authors.initials: S
authors.lastname: Uchida
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D006074:Gout Suppressants / Q000627:therapeutic use*; D006801:Humans; D033461:Hyperuricemia / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D057182:Mendelian Randomization Analysis; D027361:Organic Anion Transporters / Q000378:metabolism; D016032:Randomized Controlled Trials as Topic; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D012307:Risk Factors; D014527:Uric Acid / Q000097:blood*
chemical_list: D015415:Biomarkers; D006074:Gout Suppressants; D027361:Organic Anion Transporters; C103862:urate transporter; D014527:Uric Acid
keywords: ABCG2; Allopurinol; Benzbromarone; Chronic kidney disease; End-stage renal disease; Febuxostat; Hyperuricemia; Mendelian randomization approach; Propensity score analysis; Serum uric acid; Urate transporter