Parenteral iron therapy and phosphorus homeostasis: A review

Abstract

Phosphorus has an essential role in cellular and extracellular metabolism; maintenance of normal phosphorus homeostasis is critical. Phosphorus homeostasis can be affected by diet and certain medications; some intravenous iron formulations can induce renal phosphate excretion and hypophosphatemia, likely through increasing serum concentrations of intact fibroblast growth factor 23. Case studies provide insights into two types of hypophosphatemia: acute symptomatic and chronic hypophosphatemia, while considering the role of pre-existing conditions and comorbidities, medications, and intravenous iron. This review examines phosphorus homeostasis and hypophosphatemia, with emphasis on effects of iron deficiency and iron replacement using intravenous iron formulations.

FIGURE 1

Phosphate homeostasis in healthy individuals. ¹⁸ , ¹⁹ Phosphate loading induces fibroblast growth factor 23 (FGF23) and parathyroid hormone expression, stimulating tubular retrieval of the phosphate channel NaPi‐2a, thus limiting phosphate reabsorption. Two endocrine negative feedback loops control FGF23 expression: one involving parathyroid hormone (left) and the other involving vitamin D (right) [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 2

(A) Posttranslational cleavage of FGF23, which occurs primarily in mineralized tissue cells (eg, osteoblasts, odontoblasts and cementoblasts), is an important but not well understood regulatory mechanism that modulates the biological activity of FGF23 during iron deficiency and other pathological conditions. ²¹ (B) Assays are available to measure both total and intact FGF23 but they are not standardized or in wide clinical use. Adapted with permission from Wolf M, White KE. Coupling fibroblast growth factor 23 production and cleavage: iron deficiency, rickets, and kidney disease. Curr Opin Nephrol Hypertens. 2014;23 (4):411‐419. doi: 10.1097/01.mnh.0000447020.74593.6f ©2014 Lippincott Williams and Wilkins. Abbreviations: ADHR, autosomal dominant hypophosphatemic rickets; cFGF23, C‐terminal region of FGF23; CKD, chronic kidney disease, FGF23, fibroblast growth factor 23; hfTC; hyperphosphatemic familial tumoral calcinosis; iFGF23, intact FGF23 [Color figure can be viewed at wileyonlinelibrary.com]