The National Kidney Foundation Kidney Disease Outcome Quality Initiative (KDOQI) recommends targeting Hb between 11.0 and 12.0 gm/dl, but evidence suggests that only 30 % of patients fall within this range at any point in time [
10]. Despite improvements, large observational studies such as the Dialysis Outcomes and Practice Patterns Study (DOPPS) indicate that anemia remains prevalent in patients receiving dialysis; therefore, there is a need to increase the proportions of patients achieving guideline Hb targets [
21]. Selection of the Hb target based on the patient’s disease state, comorbidities, and other characteristics has been an essential part of a treatment strategy [
22]. However, the risks associated with high Hb targets in recent studies [
23,
24] prompted updates to the guidelines to recommend a narrower Hb target: 110–120 g/l and not exceeding 130 g/l for most patients and 100–120 g/l for patients with type 2 diabetes mellitus (T2DM) avoiding levels above 120 g/l, particularly for those at risk of stroke [
25]. In the current study, we have chosen the target of 110–120 g/l, with a margin of ±0.5 g/l, in line with the current recommendations [
24]. The results of this study showed that both ESAs maintained the target Hb in almost 60 % of the patients, compared to the 40 % reported in large dialysis US patients [
26]. However, the results illustrate the impact of the type of ESA used in maintaining target Hb; there was a significant difference between the percentages of patient achieving target Hb in the Darbe group compared to those in Epo group, and this difference was not demonstrated before. Hemoglobin variability assessed by different statistical methods showed a tendency of better Hb stability in the Darbe group compared to the Epo group, without reaching statistically significant difference between the two groups. Fluctuations in Hb levels result in frequent under- and overshooting of targets [
27,
28]. Evidence suggests that hemoglobin variability does not only complicate maintenance of Hb within the target range, but it is also independently associated with mortality [
29,
30]. On the other hand, stability of Hb in the target level (110–120 g/l) is associated with lower 1-year mortality risk in hemodialysis patients [
29]. The number of intervention for dose changes of the long-acting Darbe group was significantly less compared to the Epo group. Data show that longer dosing intervals may lead to less variability in hemoglobin levels over time by producing fewer peaks and troughs and thereby requiring fewer dosage adjustments [
31]. The recommended dose conversion ratio on the European label (1 μg darbepoetin alfa for 200 IU Epotein alfa) was used in this study; there was a steady increase in the conversion factor, with subsequent decrease in the Darbe dose, during the study period from 200:1 at baseline to 350:1 at 6 months, with an average of 268:1 at the end of the study, with significant difference from the baseline and the end (
p < 0.001). This conversion ratio is higher than the average ratio reported in the meta-analysis of 21 studies, with 16,378 patients of 217:1 and that reported by the Canadian study of 169:1 [
32]; this difference in the conversion factor could be explained by the different design of the studies (conversion vs. straight), geographic area, quality of dialysis, and center-related anemia management practice [
33]. On the other hand, the dose of Epo remained stable during the study (
p NS). The cost of Darbe was double that of Epo (1.4 vs. 0.7 USD/kg/week); however, several factors should be taken into consideration in analyzing the cost. (1) Time saving: preliminary results of an observational study indicated that extending the administration interval from three times weekly to once weekly (QW) was associated with substantial time savings [
34]. It was estimated that 350 h of physician/nurse time per year could be saved in a center with 50 dialysis patients. If administration intervals could be successfully extended beyond QW for all patients, the resulting time savings could enable health care providers to spend more time focusing on other aspects of CKD management, including patient education, and to address other modifiable risk factors, such as hypertension and mineral balance. (2) The low conversion factor (200:1) with subsequent high doses used as the start of the study could explain in part the total high cost of Darbe; in other words, if we would have used the ratio of (350:1) from the start of the study, we would have saved 175 % of the cost. (3) From the experience of using Darbe and Epo, in cancer patients, taking into consideration the duration of clinical benefit (DCB) that is 2–7 days in Epo and 7–21 days in Darbe, one study showed, after accounting for DCB, that the average weekly cost of darbepoetin alfa was significantly lower than that of epoetin alfa ($619 vs. $940;
p < 0.001) [
35]. There was significant more vascular access thrombosis in the Epo group compared to Darbe group (12 vs. 1.4 %)
p < 0.001, and vascular access thrombosis was reported similar in Darbe and Epo groups (10 and 9 %, respectively) in a previous study comparing the efficacy and safety of Darbe to Epo [
36]. The cause of difference in the thrombosis of vascular access between the two groups in our study is not well clear, and vascular access thrombosis has been reported as a complication in dialysis patient assigned to high Hb target [
37]; in our study, the percentage of patients with Hb >125 g/l was similar in both groups (23.9, 23.3 %) and it cannot explain this phenomenon, but one can speculate that the use of decreased doses of Darbe during the study period could have a favorable impact on the access thrombosis. All biological parameters evaluated during the study were comparable between the two groups, and there was no difference between the baseline and end of the study parameters. There was no difference between the two groups in terms of number of hospitalizations and number of deaths.