{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T02:17:50Z","timestamp":1792721870311,"version":"4.5.0"},"reference-count":84,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T00:00:00Z","timestamp":1757980800000},"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>Hyperuricemia has been increasingly recognized as a modifiable contributor to chronic kidney disease (CKD) progression. Although the traditional classification of hyperuricemia distinguished between renal underexcretion and renal overload types, recent studies suggest that hyperuricemia in patients with CKD can result from heterogeneous excretory defects, including glomerular under-filtration and tubular over-reabsorption. These distinct phenotypes may drive divergent renal injury mechanisms. Experimental and clinical data reveal that monosodium urate crystals and soluble uric acid independently induce renal damage through oxidative stress, inflammasome activation, and endothelial dysfunction. Furthermore, clinical investigations showed inconsistent associations between serum uric acid levels and renal outcomes, suggesting that serum levels alone may not fully reflect urate-related renal risk. This has prompted increasing interest in uricosuric agents, particularly the selective urate reabsorption inhibitors (SURIs), which target tubular urate handling. Urate transporter 1 inhibitors have shown promise in enhancing urinary uric acid excretion and potentially preserving kidney function, especially in patients with CKD. In this review, we summarize the current evidence linking the emerging pathophysiological classification of hyperuricemia, mechanisms or urate-induced kidney injury, and therapeutic interventions. These insights may inform individualized approaches to urate-lowering therapy in CKD and support future research into phenotype-guided treatment strategies.<\/jats:p>","DOI":"10.3390\/ijms26189000","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T10:06:25Z","timestamp":1758017185000},"page":"9000","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Hyperuricemia in Chronic Kidney Disease: Emerging Pathophysiology and a Novel Therapeutic Strategy"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2959-6015","authenticated-orcid":false,"given":"Tomoaki","family":"Takata","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, Yonago, Tottori 683-8504, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukari","family":"Mae","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, Yonago, Tottori 683-8504, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shotaro","family":"Hoi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, Yonago, Tottori 683-8504, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuji","family":"Iyama","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, Yonago, Tottori 683-8504, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Isomoto","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, Yonago, Tottori 683-8504, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1093\/ndt\/gfz174","article-title":"A single number for advocacy and communication-worldwide more than 850 million individuals have kidney diseases","volume":"34","author":"Jager","year":"2019","journal-title":"Nephrol. 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