Hepcidin levels predict nonresponsiveness to oral iron therapy in patients with iron deficiency anemia

Am J Hematol. 2013 Feb;88(2):97-101. doi: 10.1002/ajh.23354. Epub 2013 Jan 18.

Abstract

Levels of hepcidin, a major regulator of iron homeostasis, may identify patients with iron deficiency anemia (IDA) who will not respond to oral iron therapy. In this study, IDA patients underwent a 14-day trial (run-in) course of ferrous sulfate therapy. Nonresponders (Hgb increase <1 g/dL with 67% compliance rate) were randomized to IV ferric carboxymaltose (FCM; two injections of 750 mg) or further oral iron for 14 days. Screening hepcidin levels were 38.4 versus 11.3 ng/mL, P = 0.0002 in nonresponders versus responders to a trial of oral iron. Hepcidin of > 20 ng/mL, showed sensitivity of 41.3%, specificity of 84.4%, and positive predictive value of 81.6% for predicting nonresponsiveness to oral iron. PPVs for ferritin> 30 ng/mL or transferrin saturation (TSAT)>15% were 59.2 and 55%, respectively. Negative predictive values for hepcidin, ferritin, and TSAT were 46.3, 22.7, and 19.7, respectively. FCM versus oral iron showed Hgb increases of ≥ 1 gm/dL in 65.3% versus 20.8% (P < 0.0001) and Hgb increases of 1.7 ± 1.3 versus 0.6 ± 0.9 g/dL (P = 0.0025), respectively. We conclude that hepcidin predicts nonresponsiveness to oral iron in patients with IDA and is superior to TSAT or ferritin for this purpose. Nonresponse to oral iron therapy does not rule out IDA, since two-thirds of patients subsequently responded to intravenous iron.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Anemia, Iron-Deficiency / blood*
  • Anemia, Iron-Deficiency / diagnosis
  • Anemia, Iron-Deficiency / diet therapy
  • Anemia, Iron-Deficiency / drug therapy*
  • Antimicrobial Cationic Peptides / blood*
  • Biomarkers / blood
  • Dietary Supplements
  • Female
  • Ferric Compounds / administration & dosage
  • Ferric Compounds / adverse effects
  • Ferric Compounds / therapeutic use*
  • Ferritins / blood
  • Ferrous Compounds / therapeutic use
  • Hemoglobins / analysis
  • Hepcidins
  • Humans
  • Injections, Intravenous
  • Iron, Dietary / therapeutic use
  • Male
  • Maltose / administration & dosage
  • Maltose / adverse effects
  • Maltose / analogs & derivatives*
  • Maltose / therapeutic use
  • Predictive Value of Tests
  • Sensitivity and Specificity
  • Transferrin / analysis
  • Transferrin / metabolism

Substances

  • Antimicrobial Cationic Peptides
  • Biomarkers
  • Ferric Compounds
  • Ferrous Compounds
  • HAMP protein, human
  • Hemoglobins
  • Hepcidins
  • Iron, Dietary
  • Transferrin
  • ferrous sulfate
  • ferric carboxymaltose
  • Maltose
  • Ferritins

Supplementary concepts

  • Iron-Refractory Iron Deficiency Anemia