{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:42:31Z","timestamp":1790811751760,"version":"4.1.0"},"reference-count":57,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,21]],"date-time":"2025-12-21T00:00:00Z","timestamp":1766275200000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Rheum Dis"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hyperuricemia, marked by elevated uric acid levels, is associated with renal disorders like acute kidney injury and chronic kidney disease, through both crystal\u2010dependent and crystal\u2010independent mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This review aims to evaluate the crystal\u2010dependent and crystal\u2010independent mechanisms by which hyperuricemia induces renal injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>A systematic review of the literature.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>Human and animal studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements<\/jats:title>\n                    <jats:p>A total of 1549 articles were initially identified from PubMed, Web of Science, Scopus, and Google Scholar. After removing 659 duplicates and screening titles and abstracts, 572 articles were excluded, and 16 could not be retrieved, leaving 302 for full\u2010text review. Of these, 17 studies met the eligibility criteria and were included. Risk of bias was assessed using SYRCLE for animal studies, ROB2 for human studies, and NOS for observational studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>From 17 studies: nine animal experiments, one human experiment, and seven observational studies. Animal studies showed hyperuricemia causes preglomerular arteriolopathy, glomerular hypertension, and worsens nephrotoxicity. Human studies demonstrated elevated uric acid, even without crystals, activates intrarenal RAS, increases oxidative stress, and reduces nitric oxide. Clinical studies confirmed high uric acid is linked to CKD progression, with very low levels also risky (\u201cJ\u2010shaped\u201d relationship). Endothelial dysfunction is a unifying mechanism, promoting inflammation and fibrosis in crystal\u2010dependent injury and vasoconstriction and renal damage in crystal\u2010independent injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This review confirmed that hyperuricemia damages the kidney through both crystal\u2010dependent and crystal\u2010independent pathways, with endothelial dysfunction as a key mediator. Further human studies are needed to confirm these findings and explore new treatments.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1756-185x.70493","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T06:05:53Z","timestamp":1766383553000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Dual Mechanisms of Hyperuricemia\u2010Associated Renal Injury: A Systematic Review of Crystal\u2010Dependent and Crystal\u2010Independent Pathways"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5982-9601","authenticated-orcid":false,"given":"Gudisa","family":"Bereda","sequence":"first","affiliation":[{"name":"Department of Pharmacy Rift Valley University  Addis Ababa Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7431-1310","authenticated-orcid":false,"given":"Felix Pius","family":"Omullo","sequence":"additional","affiliation":[{"name":"Department of Medical Services Equity Afya Limited  Lodwar Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,21]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01916-y"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12937-022-00789-7"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.649505"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2023.1190683"},{"key":"e_1_2_14_6_1","unstructured":"G. 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