Serum Erythroferrone in End Stage Renal Disease Patients: Relation to Iron Status, Anaemia and Erythropoiesis Stimulating Agents
Authors: Abdelghany Aya-tAllah Mohamad , Mohamed Amal Abd-El-Hamid , Hebah Hayam Ahmed , Salem Dalia Diaa ElDine 
Published: August 2023

Abstract

Background
Anaemia is a hallmark of chronic kidney disease (CKD), where erythropoietin deficiency and reduced iron availability by the negative iron regulator, hepcidin, are principal causes of the anaemia. Erythroferrone (ERFE), a hormone synthesized by erythroblasts, is a hepcidin inhibitor and increases iron absorption and mobilization, resulting in erythropoiesis stimulation. Thus, ERFE could be considered as one of potential clinical biomarkers for assessing erythropoiesis. Moreover, it has been found that ERFE is produced in response to erythropoietic stimulating agent (ESA) in CKD and thus could have a role in cure from anaemia in those patients. However, few studies focused on understanding the role of this hormone in the regulation of iron homeostasis.

Aim of the Work
To study the correlation between ERFE level and iron parameters and its response to iron/ESA in end stage renal disease (ESRD) patients with iron deficiency anaemia.

Study design and methods
A case-control study was carried out on 40 ESRD patients (GFR &lt; 15 ml/min/1.73 mm3) with evidence of iron deficiency anaemia. Patients were further subdivided into 2 subgroups, where subgroup I included patients who received both iron and ESA (Erythropoietin) (n = 28) and subgroup II patients who were treated with iron only (n = 12). Ten age & sex matched normal healthy subjects were included in the study as a control group. The studied parameters (ERFE, Hb, HCT%, MCV, MCH, serum iron, TSAT% and TIBC) were measured at baseline and then revaluated three months later after iron/ESA therapy. Erythroferrone was measured (baseline and post iron/ESA treatment) by ELISA.

Results
The present study was conducted on 40 ESRD patients with male to female ratio 1:1.5. Their mean age was 51.03±11.22 years and mean dry weight 73.4±13.08 Kg. The commonest risk factor was hypertension (32.5%). Treatment with iron ± EPO results in significant increase of Hb and serum iron in both patients' subgroups (p ˂ 0.001). Baseline and post treatment ERFE levels were higher in patients’ groups than in the control group with significant statistical difference (p = 0.016 & 0.023 respectively). The highest level was in those patients treated with both iron and EPO (212.31±106.33 ng/L at baseline & 520.00±255.26 post treatment). Positive correlation of ERFE level with both Hb and serum Iron (p-value &lt;0.05) was detected.

Conclusion
Managing anaemia in ESRD patients remain a significant unmet challenge in those patients. Insight into iron homeostasis is important in order to develop new diagnostic as well as therapeutic modalities. Our study proved that ERFE is associated with iron/EPO therapy and positively correlated with hemoglobin and serum iron levels. Thus, ERFE could play a key role in the assessment of erythropoietic activity, as well as, in the treatment process among those patients in status of iron deficiency or iron overload.