BACKGROUND:
Hepcidin, a liver-derived
peptide induced by
iron overload and
inflammation, is a major regulator of
iron homeostasis. As
hepcidin decreases
gastrointestinal iron absorption and recirculation from
monocytes, over-expression is associated with the development of
anaemia. METHODS: We studied the associations between circulating
hepcidin levels and various laboratory parameters related to
anaemia and/or
inflammation in 20 patients on chronic
haemodialysis. Furthermore, we determined the impact of
dialysis and
iron and/or
erythropoietin (rhEpo) supplementation therapy on
hepcidin serum concentrations. The patients were withheld from
iron and rhEpo for 2 weeks before study entry.
Hepcidin was measured by
liquid chromatography-mass spectrometry (LC-MS/MS);
serum iron and
haematological parameters,
cytokines and pro-hepcidin by commercially available
enzyme-linked immunosorbent assays (
ELISA) or standard automated methods. RESULTS: While
hepcidin levels at baseline were not
correlated to pro-hepcidin, interleukin-6 or
transforming growth factor-beta concentrations, we found significant associations with
reticulocyte count (r = -0.55; P = 0.015),
serum iron (r = 0.7; P = 0.004) and
ferritin levels (r = 0.63; P = 0.004) and
transferrin saturation (r = 0.69, P = 0.001).
Dialysis using either a high or a low flux biocompatible
dialyser resulted in a significant decrease of
hepcidin concentrations, which returned to pre-dialysis values before the next
dialysis session. When studying the effects of
anaemia treatment, we observed a
significant reduction of
hepcidin levels following administration of rhEpo but not
iron. CONCLUSIONS:
Hepcidin levels in stable
haemodialysis patients appear to reflect systemic
iron load, but not
inflammation. Due to the negative association between
reticulocyte counts and
hepcidin, the reduction of circulating
hepcidin concentrations by
dialysis and/or rhEpo treatment may positively affect
erythropoiesis.
