Iron, inflammation, and fibroblast growth factor 23: Integrating molecular crosstalk, cardiovascular biology, and therapeutic perspectives

This narrative review examines how iron availability, inflammation, and erythropoiesis regulate fibroblast growth factor 23 (FGF23), and how these interactions inform cardiovascular biology and therapy.The central framework separates FGF23 production from proteolytic processing: Increased synthesis can coexist with efficient cleavage and little change in intact hormone, whereas insufficient cleavage permits biologically active FGF23 to accumulate.C-terminal assays detect both intact hormone and cleavage products and therefore require different interpretation from intact assays.Experimental studies identify erythroid cells as an inducible FGF23 source and suggest distinct actions of intact FGF23 and C-terminal fragments on erythropoiesis, inflammation, and iron availability.Cellular and animal studies also support cardiac and vascular effects, but inconsistent experimental findings, heterogeneous assays, and predominantly observational human evidence limit causal inference.Iron repletion generally reduces the stimulus for FGF23 production, whereas ferric carboxymaltose can increase intact FGF23 and cause renal phosphate wasting.Global FGF23 neutralization caused hyperphosphatemia, vascular calcification, and increased mortality in experimental chronic kidney disease.Correcting upstream disturbances and testing selective signaling interventions are therefore priorities, but cardiovascular efficacy and safety remain unproven.