Hepcidin is not useful as a biomarker for iron needs in haemodialysis patients on maintenance erythropoiesis-stimulating agents.
BACKGROUND
It has been suggested that hepcidin may be useful as a tool for managing iron therapy in haemodialysis (HD) patients on erythropoiesis-stimulating agents (ESA).


METHODS
We used SELDI-TOF mass spectrometry assay to measure serum hepcidin-25 (Hep-25) and hepcidin-20 (Hep-20) in 56 adult HD patients on maintenance ESA to assess their ability to predict haemoglobin (Hb) response after 1 g intravenous iron (62.5 mg ferric gluconate at 16 consecutive dialysis sessions) and their relationship with markers of iron status, inflammation and erythropoietic activity.


RESULTS
At multivariate analysis (in a model that also included Hb, reticulocyte, ESA dose, HFE genotype, soluble transferrin receptor [sTfR] and C-reactive protein), Hep-25 independently correlated with ferritin (β = 0.03, P = 0.01) and the percentage of hypochromic red blood cells [%Hypo] (β = 1.84, P = 0.01), suggesting that Hep-25 may be a useful biomarker for iron stores and bone marrow iron availability. Hep-20 correlated independently with Hep-25 (β = 0.159, P < 0.001) and ferritin (β = 0.006, P = 0.05), suggesting that it may be a useful additional biomarker for iron stores. On receiver operating characteristics curve analysis, neither Hep-25 nor Hep-20 significantly predicted who will increase their Hb after iron loading (AUC = 0.52 ± 0.09 and 0.54 ± 0.08, P = 0.612), and the same applied to ferritin and transferrin saturation (AUC = 0.55 ± 0.08 and 0.59 ± 0.08, P = 0.250), whereas %Hypo and reticulocyte Hb content were significant predictors (AUC = 0.84 ± 0.05 and 0.70 ± 0.08, P < 0.01). At multivariate logistic regression analysis, %Hypo was the only biomarker independently associated with iron responsiveness.


CONCLUSIONS
Although our study suggests an important role for hepcidin in regulating iron homeostasis in HD patients on ESA, our findings do not support its utility as a predictor of iron needs, offering no advantage over established markers of iron status.
Hemodialysis Unit Ospedale Policlinico, Division of Nephrology, University of Verona, Verona, Italy. nicola.tessitore@ospedaleuniverona.it
Nicola
N
Tessitore
Domenico
D
Girelli
Natascia
N
Campostrini
Valeria
V
Bedogna
Giovanni
G
Pietro Solero
Annalisa
A
Castagna
Edoardo
E
Melilli
William
W
Mantovani
Giovanna
G
De Matteis
Oliviero
O
Olivieri
Albino
A
Poli
Antonio
A
Lupo
D000368:Aged; D000369:Aged, 80 and over; D018798:Anemia, Iron-Deficiency / Q000097:blood / Q000517:prevention & control*; D023181:Antimicrobial Cationic Peptides / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D005260:Female; D006397:Hematinics / Q000627:therapeutic use*; D006454:Hemoglobins / Q000378:metabolism; D064451:Hepcidins; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007275:Injections, Intravenous; D007501:Iron / Q000008:administration & dosage / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D006435:Renal Dialysis; D012189:Retrospective Studies; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D023181:Antimicrobial Cationic Peptides; D015415:Biomarkers; C578702:HAMP protein, human; D006397:Hematinics; D006454:Hemoglobins; D064451:Hepcidins; D007501:Iron