Parenteral iron polymaltose changes i:c-terminal FGF23 ratios in iron deficiency, but not in dialysis patients

BACKGROUND/OBJECTIVES: Iron and phosphate are both vital to many biological cellular processes with central roles in energy metabolism, cellular proliferation and nucleic acid synthesis. Regulatory pathways in some of these metabolic pathways may intersect at fibroblast growth factor 23 (FGF23), a major phosphate regulatory hormone. Iron is reported to induce hypophosphataemia in rare cases, and recent reports suggest that iron deficiency may upregulate FGF23 synthesis by mechanisms involving hypoxia-inducible factor 1 alpha (HIF1 alpha). Our objective was to evaluate the effect of administration of intravenous iron polymaltose on intact and c-terminal FGF23 (i: cFGF23) ratios in two independent cohorts of patients, iron-deficient but non-inflamed patients and haemodialysis (HD)-dependent patients, and to examine the balance of synthesis and degradation. SUBJECTS/METHODS: We studied biochemical effects of intravenous iron polymaltose on both iFGF23 and cFGF23 fragments and their ratios in two patient groups: iron-deficient patients with normal renal function (ID-norm) and HD patients receiving iron supplementation (HD-ESKD) at a single institution. Patients were tested at baseline, day 4 and day 12 post iron administration. RESULTS: Parenteral iron polymaltose resulted in increased i: cFGF23 ratios in ID-norm patients where circulating cFGF23 levels decreased with no appreciable effect on iFGF23, whereas no significant changes in i: cFGF23 ratios were observed in HD-ESKD patients following intravenous administration of 100mg iron polymaltose. CONCLUSIONS: Dysregulation of intracellular FGF23-processing mechanisms may be related to iron deficiency per se rather than iron repletion with iron polymaltose. In ID-norm, i: cFGF23 ratios altered with iron administration without significant clinical alterations in mineral parameters, implying that other regulatory mechanisms may be important. Finally, iron supplementation in HD-ESKD patients does not appear to significantly affect i: cFGF23 ratios already disturbed by a chronic inflammatory or functionally iron-deficient state.