Phosphate and Inflammation in Health and Kidney Disease

作者：Novillo-Sarmiento C, García-Sáez RM, Rivas-Domínguez A, Torralba-Duque A, Rodelo-Haad C, Rodríguez-Ortiz ME, Muñoz-Castañeda JR, Pendón-RuizdeMier MV · 发表于：International journal of molecular sciences · 年份：2025 · DOI：10.3390/ijms27010408 · 被引用次数：66 · 研究领域：Phosphates、Renal Insufficiency, Chronic、Inflammation、Humans、Animals、Atherosclerosis、Oxidative Stress、Malnutrition、Micronutrients、Vascular Calcification、Vascular Remodeling

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 "Phosphatopathy", 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/β-catenin and TGF-β signaling, and disrupts the FGF23-Klotho axis, promoting endothelial dysfunction, vascular calcification, and left ventricular hypertrophy (LVH). These pathways converge with systemic inflammation and energy imbalance, contributing to the malnutrition-inflammation-atherosclerosis (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-rather than serum phosphate alone-include 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 rede...