FIGURE 3.

Comparative labile iron pools of parenteral iron products. (A) FGF23 is a circulating hormone that is synthesized primarily in osteocytes and osteoblasts, and is inactivated by cleavage. Under physiologic circumstances and following iron repletion, synthesis and cleavage are coupled to maintain circulating level within a set range. With iron deficiency, FGF23 gene transcription is increased, but additional synthesis of FGF23 is offset by increased cleavage to maintain normal circulating levels of active FGF23. (B) FCM appears to uncouple the balance between synthesis and inactivation, resulting in increased circulating intact FGF23. The mechanism is unknown, but proposed mechanisms include inhibition of cleavage in osteocytes or activation of FGF23 production in sites without the FGF23 cleavage apparatus. High circulating FGF23 directly inhibits phosphate reabsorption in the proximal tubules of the kidney, and reduces production of serum 1,25‐dihydroxyvitamin D, which in turn reduces dietary phosphate and calcium absorption. Decreased serum calcium increases PTH production to maintain serum calcium homeostasis; PTH also inhibits phosphate reabsorption. The net result is increased phosphate excretion by the kidney and potential for hypophosphatemia. FCM, ferric carboxymaltose; FGF23, fibroblast growth factor‐23; PTH, parathyroid hormone [Color figure can be viewed at wileyonlinelibrary.com]