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Medicina is published by MDPI from Volume 54 Issue 1 (2018). Articles in this Issue were published by another publisher in Open Access under a CC-BY (or CC-BY-NC-ND) licence. Articles are hosted by MDPI on mdpi.com as a courtesy and upon agreement with Lithuanian Medical Association, Lithuanian University of Health Sciences, and Vilnius University.
Open AccessArticle
Medicina 2017, 53(2), 90-100; https://doi.org/10.1016/j.medici.2017.03.001 (registering DOI)

Hepcidin serum levels and resistance to recombinant human erythropoietin therapy in hemodialysis patients

1
Department of Nephrology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania
2
Department of Odontology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania
*
Author to whom correspondence should be addressed.
Received: 25 June 2015 / Revised: 25 November 2016 / Accepted: 20 March 2017 / Published: 31 March 2017
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Abstract

Objective: The aim of this study was to analyze the factors that are associated with the response to erythropoiesis-stimulating agents (ESAs) and its association with hospitalization and mortality rates; to evaluate the serum hepcidin level and its associations with iron profile, inflammatory markers, ESA responsiveness, and mortality; and to determine independent factors affecting ERI and hepcidin.Materials and methods: To evaluate a dose-response effect of ESAs we used the erythropoietin resistance index (ERI). Patients were stratified in two groups: nonresponders and responders (ERI > 15, n = 20, and ERI ≤15 U/kg/week/g per 100 mL, n = 153, respectively). Hematological data, hepcidin levels, iron parameters, inflammatory markers, hospitalization and mortality rates were compared between the groups. Multiple regression analysis was used to determine independent factors affecting ERI and hepcidin.Results: C-reactive protein (CRP) (β = 0.078, P = 0.007), albumin (β = 0.436, P = 0.004), body mass index (β = 0.374, P < 0.001), and hospitalization rate per year (β = 3.017, P < 0.001) were found to be significant determinants of ERI in maintenance hemodialysis (MHD) patients. Inadequate dialysis was associated with higher ERI. Patients with concomitant oncological diseases had higher ERI (31.2 ± 12.4 vs 9.7 ± 8.1 U/kg/week/g per 100 mL, P = 0.002). The hepcidin level was 158.51 ± 162.57 and 120.65 ± 67.28 ng/mL in nonresponders and responders, respectively (P = 0.33). Hepcidin correlated directly with ERI, dose of ESAs, ferritin and inversely with Hb, transferrin saturation, and albumin. ERI (β = 4.869, P = 0.002) and ferritin (β = 0.242, P = 0.003) were found to be significant determinants of hepcidin in MHD patients. The hospitalization rate per year was 2.35 ± 1.8 and 1.04 ± 1.04 in nonresponders and responders, respectively (P = 0.011). The mean length of one hospitalization was 25.12 ± 21.26 and 10.82 ± 17.25 days, respectively (P = 0.012). Death occurred in 30% of the patients from the responders' group and in 50% from the nonresponders' group (P = 0.289). The mean hepcidin concentration of patients who died was 141.9 ± 129.62 ng/mL and who survived, 132.98 ± 109.27 ng/mL (P = 0.797).Conclusions: CRP, albumin, BMI, and hospitalization rate per year were found to be significant determinants of ERI in MHD patients. Inadequate dialysis was associated with higher epoetin requirements. There were no difference in patient mortality by ERI, but a significant difference in hospitalization rates and mean length of one hospitalization was revealed. A significant positive relation between hepcidin and ERI was revealed. ERI and ferritin were found to be significant determinants of hepcidin in MHD patients. Hepcidin was not related to mortality.
Keywords: Renal anemia; Resistance; Erythropoiesis-stimulating agents; Hepcidin; Inflammation Renal anemia; Resistance; Erythropoiesis-stimulating agents; Hepcidin; Inflammation
This is an open access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives License (CC BY-NC-ND) (CC BY-NC-ND).

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Petrulienė, K.; Žiginskienė, E.; Kuzminskis, V.; Nedzelskienė, I.; Bumblytė, I.A. Hepcidin serum levels and resistance to recombinant human erythropoietin therapy in hemodialysis patients. Medicina 2017, 53, 90-100.

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