In hemodialysis patients erythroferon, hepidin levels and ironinvestigation of the relationship of the parameters

Introduction: Anemia is a major problem in chronic kidney disease (CKD) patients. The most important reason is the relative low erythropoietin (EPO) level however here are many factors that contribute to anemia, such as absolute iron deficiency, inflammation, and increased hepcidin. There are studies suggesting that erythroferron (ERFE), a protein released from erythroblasts after EPO stimulation, suppresses hepcidin release. In our study, we aimed to investigate erythroferron, hepcidin, erythropoietin levels and iron parameters in hemodialysis patients who received two different erythropoiesis stimulating agents (ESA), as epoetin alpha and darbopoetin alpha compared to patients who were not given ESA. We also aimed to examine the changes in these parameters over time following ESA administration in patients receiving treatment. Material and Method: In our prospective study, 60 patients undergoing hemodialysis were classified into 3 groups, those who did not receive ESA, those who received epoetin alpha and those who received darbepoetin alpha, and were examined in two stages. In the first stage, the relationship between hepcidin and ERFE levels and demographic data, CKD etiology, dialysis time, hemogram, iron parameters, and EPO levels were investigated in these three groups. In the second stage, the investigation continued with patients using only ESA. In these patients, blood samples were taken again just before ESA administration and on the 2nd and 7th days before hemodialysis. The change in EPO, hepcidin and ERFE levels and the relationship of these levels with each other, hemogram and iron parameters were tried to be revealed. Results: The patient groups were similar in terms of age, gender, CKD duration, duration of hemodialysis, kidney functions, hemogram and iron parameters, but C-reactive protein (CRP) level was higher in the epoetin alfa group than in the other groups. There was no significant difference between the groups in terms of hepcidin and ERFE levels. EPO level was lower in the group that did not receive ESA, as expected, and in the other two groups it was similar. In the evolvation performed after the ESA application, it was observed that the EPO level increased numerically in both groups on the 2nd day, and decreased again on the 7th day and decreased to similar basal levels, but this change was statistically significant only in the epoetin alfa group (<0.001). Although it was observed that the level of hepcidin increased gradually on the 2nd and 7th days, this change was statistically significant in the epoetin group, and the increase in hepcidin on the 2nd day did not reach statistical significance in the darbepoetin group (0, 2, and 7th day in the epoetin group, respectively, 5,7, 6.18, 7,54 ng\ml, p<0.001; and in the darbepoetin group, respectively, 5,3, 6,75, 8,01 ng\ml, p=0.006). Although ERFE levels were also tended to increase numerically, this increase did not reach statistical significance (in the epoetin group, 0, 2 and 7 days, respectively, 0,62, 0,64, 0,73 ng\ml, p=0.072; in the darbepoetin group, respectively, 0,5, 0,51, 0,89 ng\ml, p=0,069). Both hepcidin and ERFE levels at day 0, 2, and 7 were not different between groups. Conclusion: ERFE levels, which were suggested to increase with endogenous and exogenous EPO stimulation in animal studies and studies conducted in other patient groups, were found to be similar across groups in hemodialysis patients who did not receive ESA and who received different ESAs in our study. Again, no difference was found between the groups in terms of hepcidin level, which is thought to be suppressed by ERFE, but after ESA administration, hepcidin levels increased progressively, especially in the epoetin group, where basal CRP was high. As reflecting the multiple factors and complex mechanisms affecting erythropoiesis in end-stage CKD patients, the few ERFE studies in this patient group report conflicting results. In our study, ERFE levels changed in a very narrow range after ESA and although an increasing trend was observed in both groups, it did not reach statistical significance. The significant and negative correlation between the increase in ERFE and the amount of increase in hepcidin in the first days suggests that there may be a relationship that could not be clearly revealed due to the limitations of the study, such as the small number of patients and the small number of consecutive measurements. Keywords: Chronic kidney disease, hemodialysis, anemia, erythropoiesis stimulating agents, erythropoietin, hepcidin, erythroferrone