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J. Clin. Med. 2019, 8(4), 523; https://doi.org/10.3390/jcm8040523

Serum Erythroferrone Levels Associate with Mortality and Cardiovascular Events in Hemodialysis and in CKD Patients: A Two Cohorts Study

1
CNR-IFC, Clinical Epidemiology of Renal Diseases and Hypertension, Reggio Cal Unit, 89126, Italy
2
Corvidia, Waltham (MA), 02451, USA
*
Author to whom correspondence should be addressed.
Received: 7 March 2019 / Revised: 5 April 2019 / Accepted: 5 April 2019 / Published: 16 April 2019
(This article belongs to the Section Nephrology & Urology)
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Abstract

Erythroferrone (ERFE) is a hepcidin inhibitor whose synthesis is stimulated by erythropoietin, which increases iron absorption and mobilization. We studied the association between serum ERFE and mortality and non-fatal cardiovascular (CV) events in a cohort of 1123 hemodialysis patients and in a cohort of 745 stage 1–5 chronic kidney disease (CKD) patients. Erythroferrone was measured by a validated enzyme-linked immunosorbent assay (ELISA). In the hemodialysis cohort, serum ERFE associated directly with erythropoiesis stimulating agents (ESA) dose (p < 0.001) and inversely with serum iron and ferritin (p < 0.001). Erythroferrone associated with the combined outcome in an analysis adjusting for traditional risk factors, factors peculiar to end-stage kidney disease, serum ferritin, inflammation, and nutritional status (HR, hazard ratio, (5 ng/mL increase: 1.04, 95% confidence interval, CI: 1.01–1.08, p = 0.005). Furthermore, treatment with ESA modified the relationship between ERFE and the combined end-point in adjusted analyses (p for the effect modification = 0.018). Similarly, in CKD patients there was a linear increase in the risk for the same outcome in adjusted analyses (HR (2 ng/mL increase): 1.04, 95% CI: 1.0–1.07, p = 0.015). Serum ERFE is associated with mortality and CV events in CKD and in HD patients, and treatment by ESA amplifies the risk for this combined end-point in HD patients.
Keywords: erythroferrone; chronic kidney disease; dialysis; mortality; iron erythroferrone; chronic kidney disease; dialysis; mortality; iron
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Spoto, B.; Kakkar, R.; Lo, L.; Devalaraja, M.; Pizzini, P.; Torino, C.; Leonardis, D.; Cutrupi, S.; Tripepi, G.; Mallamaci, F.; Zoccali, C. Serum Erythroferrone Levels Associate with Mortality and Cardiovascular Events in Hemodialysis and in CKD Patients: A Two Cohorts Study. J. Clin. Med. 2019, 8, 523.

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