{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T15:44:19Z","timestamp":1792424659364,"version":"4.5.0"},"reference-count":66,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T00:00:00Z","timestamp":1767052800000},"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>Phosphate is emerging as an active mediator of oxidative stress and vascular injury in chronic kidney disease (CKD). This emerging pathophysiological framework, referred to as \u201cPhosphatopathy\u201d, describes the systemic syndrome driven by chronic phosphate overload and characterized by oxidative stress, inflammation, endothelial dysfunction, vascular calcification, cellular senescence, and metabolic imbalance. Beyond being a biochemical marker, phosphate overload triggers NOX-derived reactive oxygen species (ROS), activates Wnt\/\u03b2-catenin and TGF-\u03b2 signaling, and disrupts the FGF23\u2013Klotho axis, promoting endothelial dysfunction, vascular calcification, and left ventricular hypertrophy (LVH). These pathways converge with systemic inflammation and energy imbalance, contributing to the malnutrition\u2013inflammation\u2013atherosclerosis (MIA) syndrome. Experimental and clinical data reveal that the phosphate\/urinary urea nitrogen (P\/UUN) ratio is a sensitive biomarker of inorganic phosphate load, while emerging regulators such as microRNA-125b and calciprotein particles integrate phosphate-driven oxidative and inflammatory responses. Therapeutic strategies targeting phosphate burden\u2014rather than serum phosphate alone\u2014include dietary restriction of inorganic phosphate, non-calcium binders, magnesium and zinc supplementation, and activation of important pathways related to the activation of antioxidant defense such as AMP-activated protein kinase (AMPK) and SIRT1. This integrative framework redefines phosphate as a modifiable upstream trigger of oxidative and metabolic stress in CKD. Controlling phosphate load and redox imbalance emerges as a convergent strategy to prevent vascular calcification, improve arterial stiffness, and reduce cardiovascular risk through personalized, mechanism-based interventions.<\/jats:p>","DOI":"10.3390\/ijms27010408","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T15:30:32Z","timestamp":1767195032000},"page":"408","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Phosphate and Inflammation in Health and Kidney Disease"],"prefix":"10.3390","volume":"27","author":[{"given":"Carlos","family":"Novillo-Sarmiento","sequence":"first","affiliation":[{"name":"Unidad de Gesti\u00f3n Cl\u00ednica Nefrolog\u00eda, Reina Sofia University Hospital, 14004 Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8502-3564","authenticated-orcid":false,"given":"Raquel M.","family":"Garc\u00eda-S\u00e1ez","sequence":"additional","affiliation":[{"name":"Instituto Maim\u00f3nides de Investigaci\u00f3n Biom\u00e9dica de C\u00f3rdoba (IMIBIC), Reina Sofia University Hospital, Department of Medicine, University of Cordoba, 14004 Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Rivas-Dom\u00ednguez","sequence":"additional","affiliation":[{"name":"Instituto Maim\u00f3nides de Investigaci\u00f3n Biom\u00e9dica de C\u00f3rdoba (IMIBIC), Reina Sofia University Hospital, Department of Medicine, University of Cordoba, 14004 Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Torralba-Duque","sequence":"additional","affiliation":[{"name":"Unidad de Gesti\u00f3n Cl\u00ednica Nefrolog\u00eda, Reina Sofia University Hospital, 14004 Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8139-3840","authenticated-orcid":false,"given":"Cristian","family":"Rodelo-Haad","sequence":"additional","affiliation":[{"name":"Unidad de Gesti\u00f3n Cl\u00ednica Nefrolog\u00eda, Reina Sofia University Hospital, 14004 Cordoba, Spain"},{"name":"Instituto Maim\u00f3nides de Investigaci\u00f3n Biom\u00e9dica de C\u00f3rdoba (IMIBIC), Reina Sofia University Hospital, Department of Medicine, University of Cordoba, 14004 Cordoba, Spain"},{"name":"Redes de Investigaci\u00f3n Cooperativa Orientadas a Resultados en Salud (RICORS), Instituto de Salud Carlos III, RD24\/0004\/0004, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3696-582X","authenticated-orcid":false,"given":"Mar\u00eda E.","family":"Rodr\u00edguez-Ortiz","sequence":"additional","affiliation":[{"name":"Instituto Maim\u00f3nides de Investigaci\u00f3n Biom\u00e9dica de C\u00f3rdoba (IMIBIC), Reina Sofia University Hospital, Department of Medicine, University of Cordoba, 14004 Cordoba, Spain"},{"name":"Redes de Investigaci\u00f3n Cooperativa Orientadas a Resultados en Salud (RICORS), Instituto de Salud Carlos III, RD24\/0004\/0004, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9341-0724","authenticated-orcid":false,"given":"Juan R.","family":"Mu\u00f1oz-Casta\u00f1eda","sequence":"additional","affiliation":[{"name":"Unidad de Gesti\u00f3n Cl\u00ednica Nefrolog\u00eda, Reina Sofia University Hospital, 14004 Cordoba, Spain"},{"name":"Instituto Maim\u00f3nides de Investigaci\u00f3n Biom\u00e9dica de C\u00f3rdoba (IMIBIC), Reina Sofia University Hospital, Department of Medicine, University of Cordoba, 14004 Cordoba, Spain"},{"name":"Redes de Investigaci\u00f3n Cooperativa Orientadas a Resultados en Salud (RICORS), Instituto de Salud Carlos III, RD24\/0004\/0004, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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