Assessment of serum bioactive hepcidin-25, soluble transferrin receptor and their ratio in predialysis patients: Correlation with the response to intravenous ferric carboxymaltose.
No reliable biomarker exists to predict responsiveness to intravenous (IV) iron (Fe) in iron deficient patients with CKD. We aimed to investigate the clinical value of bioactive Hepcidin-25 and soluble Transferrin Receptor (sTfR) levels in predialysis patients.



In this prospective study 78 stable stage III-IV CKD predialysis patients with (responders) (40 patients) and without (non-responders) (38 patients) adequate erythropoiesis after IV administration of ferric-carboxymaltose (FCM). Patients were divided in two groups according to their response to IV administration of ferric-carboxymaltose (FCM). Along with measurements of common hematologic and blood chemistry parameters, determinations of sTfR and bioactive Hepcidin-25 were performed.



Hepcidin-25 levels were lower in the responders (p=0.025), while sTfR and sTfR/Hepcidin-25 ratio were higher (p<0.01 and p=0.002 respectively). Diagnostic efficacy indicated cut off point of 1.49 for Hepcidin-25 had sensitivity 84% and specificity 48%, while cut off point of 1.21 for sTfR/Hepcidin-25 ratio had sensitivity 82% and specificity 52% to predict correctly response to iron supplementation therapy. Furthermore, log sTfR/Hepcidin-25 correlated negatively with hs-CRP (p=0.005) and IL-6 (p<0.04) in non-responders, while such correlations were not found in responders (p>0.05).



These results suggest that lower Hepcidin-25, as well as higher sTfR and sTfR/Hepcidin-25 ratio were significant predictors of favorable hemoglobin response within a month after IV administration of FCM in patients with CKD. Further experiments and clinical studies in other groups of patients are needed to better elucidate the role of Hepcidin-25 and sTfR/Hepcidin-25 ratio as predictors of response to intravenous iron administration.
Renal Unit, Attikon General University Hospital, University of Athens, School of Medicine, Athens, Greece.
Athina
A
Drakou
Department of Clinical Biochemistry, "Aghia Sophia" Children's Hospital, Athens, Greece.
Alexandra
A
Margeli
Renal Unit, Attikon General University Hospital, University of Athens, School of Medicine, Athens, Greece.
Stamatia
S
Theodorakopoulou
Renal Unit, Attikon General University Hospital, University of Athens, School of Medicine, Athens, Greece.
Ioannis
I
Agrogiannis
Department of Clinical Biochemistry, "Aghia Sophia" Children's Hospital, Athens, Greece.
Christos
C
Poziopoulos
Department of Clinical Biochemistry, "Aghia Sophia" Children's Hospital, Athens, Greece. Electronic address: biochem@paidon-agiasofia.gr.
Ioannis
I
Papassotiriou
Renal Unit, Attikon General University Hospital, University of Athens, School of Medicine, Athens, Greece.
Demetrios V
DV
Vlahakos
D000368:Aged; D000369:Aged, 80 and over; D018798:Anemia, Iron-Deficiency / Q000150:complications / Q000188:drug therapy; D003956:Dialysis; D016903:Drug Monitoring / Q000379:methods; D004920:Erythropoiesis / Q000187:drug effects; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage*; D064451:Hepcidins / Q000097:blood*; D006801:Humans; D008297:Male; D008320:Maltose / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D011990:Receptors, Transferrin / Q000097:blood*; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000628:therapy; D012680:Sensitivity and Specificity
D005290:Ferric Compounds; D064451:Hepcidins; D011990:Receptors, Transferrin; C545475:hepcidin 25, human; C522335:ferric carboxymaltose; D008320:Maltose
Chronic kidney disease; Ferric carboxymaltose; Hepcidin-25; Intravenous iron administration; sTfR