Hepcidin-25 is a marker of the response rather than resistance to exogenous erythropoietin in chronic kidney disease/chronic heart failure patients

Eur J Heart Fail. 2010 Sep;12(9):943-50. doi: 10.1093/eurjhf/hfq099. Epub 2010 Jul 3.


Aims: Erythropoietin (EPO) resistance, an important cause of anaemia in patients with heart and renal failure, is associated with increased mortality. The hypothesis of the present study was that exogenous EPO decreases hepcidin levels and that the decrease in hepcidin levels upon EPO treatment is related to the bone marrow response.

Methods and results: In the EPOCARES trial, patients with renal failure (glomerular filtration rate 20-70 mL/min), heart failure, and anaemia were randomized to receive 50 IU/kg/week EPO (n = 20) or not (n = 13). Haemoglobin (Hb), hepcidin-25, ferritin, reticulocytes, serum transferrin receptor (sTfR), IL-6, and high-sensitivity C-reactive protein were measured at baseline and during treatment. Hepcidin-25 was measured by weak cation exchange chromatography/matrix assisted laser desorption ionization time-of-flight mass spectrometry. Baseline hepcidin levels were increased compared with a healthy reference population and were inversely correlated with Hb (r(2) = 0.18, P = 0.02), and positively with ferritin (r(2) = 0.51, P < 0.001), but not with renal function, high-sensitivity C-reactive protein or IL-6. Erythropoietin treatment increased reticulocytes (P < 0.001) and sTfR (P < 0.001), and decreased hepcidin (P < 0.001). Baseline hepcidin levels and the magnitude of the decrease in hepcidin correlated with the increase in reticulocytes (r(2) = 0.23, P = 0.03) and sTfR (r(2) = 0.23, P = 0.03) and also with the Hb response after 6 months (r(2) = 0.49, P = 0.001).

Conclusion: In this group of patients with combined heart and renal failure and anaemia, increased hepcidin levels were associated with markers of iron load and not with markers of inflammation. The (change in) hepcidin levels predicted early and long-term bone marrow response to exogenous EPO. In our group hepcidin seems to reflect iron load and response to EPO rather than inflammation and EPO resistance.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anemia / blood
  • Anemia / complications
  • Anemia / drug therapy*
  • Antimicrobial Cationic Peptides / blood*
  • Biomarkers / blood
  • Drug Resistance
  • Erythropoietin / administration & dosage
  • Erythropoietin / therapeutic use*
  • Female
  • Follow-Up Studies
  • Heart Failure / blood*
  • Heart Failure / complications
  • Hemoglobins / metabolism
  • Hepcidins
  • Humans
  • Kidney Failure, Chronic / blood*
  • Kidney Failure, Chronic / complications
  • Male
  • Mass Spectrometry
  • Middle Aged
  • Prognosis
  • Recombinant Proteins


  • Antimicrobial Cationic Peptides
  • Biomarkers
  • Hemoglobins
  • Hepcidins
  • Recombinant Proteins
  • hepcidin 25, human
  • Erythropoietin