No longer to be ignored: Hypophosphatemia following intravenous iron administration

Intravenous iron supplementation is increasingly used to safely and effectively correct iron deficiency anemia, but some formulations are linked to a renal phosphate wasting syndrome which is mediated by fibroblast growth factor 23. Unawareness among prescribers and the nonspecific clinical symptoms of hypophosphatemia result in underreporting of this complication. Even though it is often an asymptomatic and self-limiting condition, accumulating evidence from case reports and dedicated randomized controlled trials show that IV iron induced hypophosphatemia may be associated with clinical symptoms. If hypophosphatemia is not recognized and treated, a metabolic bone disease phenotype may develop, pathophysiologically reminiscent of hypophosphatemic rickets as seen in X-linked hypophosphatemic rickets or oncogenic osteomalacia. This syndrome is particularly, but not uniquely, associated with formulations containing ferric carboxymaltose, probably due to specific chemical characteristics of its carbohydrate moiety. Risk factors include repeated infusion, severity of iron deficiency, as well as normal kidney function. Coexisting vitamin D deficiency or hyperparathyroidism increase the risk of metabolic bone disease. Complications can be easily prevented by an early diagnosis and switching to another IV iron formulation. In this review, we describe the epidemiology and pathophysiology of this condition, to raise awareness among prescribing clinicians.