Hepcidin-25 is related to cardiovascular events in chronic haemodialysis patients

Nephrol Dial Transplant. 2013 Dec;28(12):3062-71. doi: 10.1093/ndt/gfs488. Epub 2012 Nov 11.


Background: The development of atherosclerosis may be enhanced by iron accumulation in macrophages. Hepcidin-25 is a key regulator of iron homeostasis, which downregulates the cellular iron exporter ferroportin. In haemodialysis (HD) patients, hepcidin-25 levels are increased. Therefore, it is conceivable that hepcidin-25 is associated with all-cause mortality and/or fatal and non-fatal cardiovascular (CV) events in this patient group. The aim of the current analysis was to study the relationship between hepcidin-25 and all-cause mortality and both fatal and non-fatal CV events in chronic HD patients.

Methods: Data from 405 chronic HD patients included in the CONvective TRAnsport STudy (NCT00205556) were studied (62% men, age 63.7 ± 13.9 years [mean ± SD]). The median (range) follow-up was 3.0 (0.8-6.6) years. Hepcidin-25 was measured with mass spectrometry. The relationship between hepcidin-25 and all-cause mortality or fatal and non-fatal CV events was investigated with multivariate Cox proportional hazard models.

Results: Median (interquartile range) hepcidin-25 level was 13.8 (6.6-22.5) nmol/L. During follow-up, 158 (39%) patients died from any cause and 131 (32%) had a CV event. Hepcidin-25 was associated with all-cause mortality in an unadjusted model [hazard ratio (HR) 1.14 per 10 nmol/L, 95% CI 1.03-1.26; P = 0.01], but not after adjustment for all confounders including high-sensitive C-reactive protein (HR 1.02 per 10 nmol/L, 95% CI 0.87-1.20; P = 0.80). At the same time, hepcidin-25 was significantly related to fatal and non-fatal CV events in a fully adjusted model (HR 1.24 per 10 nmol/L, 95% CI 1.05-1.46, P = 0.01).

Conclusion: Hepcidin-25 was associated with fatal and non-fatal CV events, even after adjustment for inflammation. Furthermore, inflammation appears to be a significant confounder in the relation between hepcidin-25 and all-cause mortality. These findings suggest that hepcidin-25 might be a novel determinant of CV disease in chronic HD patients.

Keywords: cardiovascular events; haemodialysis; hepcidin-25; inflammation; mortality.

Publication types

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

MeSH terms

  • Biomarkers / metabolism*
  • C-Reactive Protein / metabolism
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / metabolism*
  • Cardiovascular Diseases / mortality
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Hepcidins / metabolism*
  • Humans
  • Inflammation / etiology
  • Inflammation / metabolism
  • Inflammation / mortality
  • Kidney Failure, Chronic / complications*
  • Male
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Renal Dialysis / adverse effects*
  • Survival Rate


  • Biomarkers
  • Hepcidins
  • hepcidin 25, human
  • C-Reactive Protein