Iron-induced hypophosphatemia: an emerging complication

Curr Opin Nephrol Hypertens. 2017 Jul;26(4):266-275. doi: 10.1097/MNH.0000000000000329.

Abstract

Purpose of review: Iron-induced hypophosphatemia is a well documented side-effect but associated complications are largely neglected, because the results from single dosing studies suggest that transient decreases in plasma phosphate concentrations are asymptomatic and fully reversible. However, an increasing number of case reports and case series suggest that some patients develop severe and symptomatic hypophosphatemia. Long-term complications from hypophosphatemia include osteomalacia and bone fractures, which can result from repeated intravenous administration of certain high-dose iron preparations.

Recent findings: Results from clinical trials suggest that the highest risk for the development of hypophosphatemia is associated with ferric carboxymaltose, iron polymaltose, and saccharated iron oxide. Clinical studies show that renal phosphate wasting mediated by increased fibroblast growth factor 23 causes hypophosphatemia after iron therapy. Impaired renal function therefore protects from hypophosphatemia, whereas the highest incidences and most severe manifestations have been reported in patients in whom the underlying cause of iron deficiency cannot be corrected.

Summary: Diagnosis of iron-induced hypophosphatemia requires clinical suspicion. Treatment is guided by the severity of hypophosphatemia, and most patients will require oral or intravenous phosphate substitution. Future treatment options could involve therapeutic anti-FGF23 antibody (KRN23). Prevention and correction of vitamin D deficiency represents a supportive treatment option.

Publication types

  • Review

MeSH terms

  • Administration, Intravenous
  • Fractures, Bone / etiology
  • Humans
  • Hypophosphatemia / chemically induced*
  • Hypophosphatemia / diagnosis
  • Hypophosphatemia / physiopathology
  • Hypophosphatemia / therapy
  • Iron Compounds / administration & dosage
  • Iron Compounds / adverse effects*
  • Iron Compounds / metabolism
  • Osteomalacia / etiology

Substances

  • Iron Compounds