{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T04:06:43Z","timestamp":1792037203654,"version":"4.4.0"},"reference-count":116,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T00:00:00Z","timestamp":1629936000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Uric acid (UA) is synthesized mainly in the liver, intestines, and vascular endothelium as the end product of an exogenous purine from food and endogenously from damaged, dying, and dead cells. The kidney plays a dominant role in UA excretion, and the kidney excretes approximately 70% of daily produced UA; the remaining 30% of UA is excreted from the intestine. When UA production exceeds UA excretion, hyperuricemia occurs. Hyperuricemia is significantly associated with the development and severity of the metabolic syndrome. The increased urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) expression, and glycolytic disturbances due to insulin resistance may be associated with the development of hyperuricemia in metabolic syndrome. Hyperuricemia was previously thought to be simply the cause of gout and gouty arthritis. Further, the hyperuricemia observed in patients with renal diseases was considered to be caused by UA underexcretion due to renal failure, and was not considered as an aggressive treatment target. The evidences obtained by basic science suggests a pathogenic role of hyperuricemia in the development of chronic kidney disease (CKD) and cardiovascular diseases (CVD), by inducing inflammation, endothelial dysfunction, proliferation of vascular smooth muscle cells, and activation of the renin-angiotensin system. Further, clinical evidences suggest that hyperuricemia is associated with the development of CVD and CKD. Further, accumulated data suggested that the UA-lowering treatments slower the progression of such diseases.<\/jats:p>","DOI":"10.3390\/ijms22179221","type":"journal-article","created":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T09:27:57Z","timestamp":1629970077000},"page":"9221","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":573,"title":["Molecular Biological and Clinical Understanding of the Pathophysiology and Treatments of Hyperuricemia and Its Association with Metabolic Syndrome, Cardiovascular Diseases and Chronic Kidney Disease"],"prefix":"10.3390","volume":"22","author":[{"given":"Hidekatsu","family":"Yanai","sequence":"first","affiliation":[{"name":"Department of Diabetes, Endocrinology and Metabolism, National Center for Global Health and Medicine Kohnodai Hospital, 1-7-1 Kohnodai, Chiba 272-8516, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Adachi","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Endocrinology and Metabolism, National Center for Global Health and Medicine Kohnodai Hospital, 1-7-1 Kohnodai, Chiba 272-8516, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariko","family":"Hakoshima","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Endocrinology and Metabolism, National Center for Global Health and Medicine Kohnodai Hospital, 1-7-1 Kohnodai, Chiba 272-8516, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisayuki","family":"Katsuyama","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Endocrinology and Metabolism, National Center for Global Health and Medicine Kohnodai Hospital, 1-7-1 Kohnodai, Chiba 272-8516, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.jare.2017.03.003","article-title":"Physiological functions and pathogenic potential of uric acid: A review","volume":"8","author":"Tallima","year":"2017","journal-title":"J. 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