{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:54:32Z","timestamp":1790877272882,"version":"4.1.0"},"reference-count":116,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["24CDA1268434"],"award-info":[{"award-number":["24CDA1268434"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institutes of Health National Heart, Lung, and Blood Institute","award":["R01HL133179"],"award-info":[{"award-number":["R01HL133179"]}]},{"name":"National Institutes of Health National Heart, Lung, and Blood Institute","award":["R01HL159994"],"award-info":[{"award-number":["R01HL159994"]}]},{"name":"Cardiology Division startup and the Pak Center Endowed Professor Collaborative Support Grant at UT Southwestern Medical Center"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hypertension remains a major public health concern globally. Accumulating evidence suggests that dietary phosphate (Pi) and fibroblast growth factor 23 (FGF23), a phosphaturic hormone, are involved in blood pressure regulation. Experimental studies have shown that excess Pi consumption, largely from inorganic Pi used as a preservative or flavor enhancer in processed foods, and increased FGF23 may contribute to vascular abnormalities, thereby promoting hypertension. Importantly, recent animal studies have demonstrated that peripheral FGF23 can cross the blood\u2013brain barrier and stimulate FGF receptor 4 (FGFR4)-calcineurin signaling in the brain, contributing to sympathetic overactivation and hypertensive responses during high Pi loading. Additionally, dietary Pi loading leads to suppression of Klotho, which may further contribute to hypertension. Such mechanisms are potentially relevant to chronic kidney disease (CKD), a condition characterized by Pi retention, massively elevated FGF23, sympathetic overactivity, and hypertension. This review highlights current evidence linking Pi-induced FGF23 pathogenically to hypertension, with focus on FGF23 translocation to and FGFR4 signaling in the central nervous system as a potential mechanism and therapeutic target for hypertension associated with high Pi intake and CKD.<\/jats:p>","DOI":"10.3390\/ijms27031138","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T09:16:59Z","timestamp":1769159819000},"page":"1138","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["High-Phosphate-Induced Hypertension: The Pathogenic Role of Fibroblast Growth Factor 23 (FGF23) Signaling in Sympathetic Nervous System Activation"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1048-9543","authenticated-orcid":false,"given":"Han-Kyul","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Internal Medicine-Cardiology Division-Hypertension Section, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA"},{"name":"Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orson W.","family":"Moe","sequence":"additional","affiliation":[{"name":"Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA"},{"name":"Department of Internal Medicine-Nephrology Division, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA"},{"name":"Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanpen","family":"Vongpatanasin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine-Cardiology Division-Hypertension Section, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA"},{"name":"Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,23]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2023). 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