All our patients had been on ESAs and intravenous iron therapy since HD initiation and they had to have been on HD for at least 3 months as a prerequisite to be included in the study. Despite this, 59.7% of them had Hb < 11g/dl at the time of enrollment. Throughout the study this percentage fluctuated between 52.9% and 68.2%. Our data are comparable to the values reported by the 2001 North American Pediatric Renal Trials and Cooperative Studies (NAPRTCS) [5, 6], and higher compared to values reported by Frankenfield et al. [7] and Fadrowski et al. [8]. On the other hand, 99% of Sudanese children on HD were anemic despite extensive use of rHuEPO and iron supplementation [9].

We did not find any association between the presence of anemia and each of age, sex, and cause of CKD. Abdelmageed et al. [9] reported similar results. Fadrowski et al. [8] found the same results except that they showed an increase in anemia as age increased. There was significant association between the presence of anemia in our patients at the time of enrollment into the study and HD duration < 6 months. Abdelmageed et al. [9] and Fadrowski et al. [8] reported the same finding. We did not find any association between the presence of anemia and either spKt/V or any of the HD modalities. Fadrowski et al. [8] and Smith et al. [10] reported the same regarding spKt/V and anemia.

Serum ferritin and TSAT are the most commonly used measurements to determine iron status in patients on regular HD. Absolute iron deficiency anemia was found in 1.8–4.5% of our patients. Abdelmageed et al. [9] reported absolute iron deficiency in 4.17% of their patients. Like ours, Fadrowski et al. [8] did not show any significant association between the presence of anemia and TSAT or serum ferritin. According to Gaweda [11], due to biological and analytic variability of TSAT and serum ferritin, single measurements had limited diagnostic value in evaluating iron status in HD patients and they should be measured at quarterly intervals, just as we did in our study.

One of the reasons for rhEPO-resistant anemia in CKD patients might be attributed to functional iron deficiency associated with impaired iron availability [12]. In our cohort, however, only 2.4–4.2% of anemic patients fulfilled the criteria for functional iron deficiency. In HD patients, functional iron deficiency anemia could be attributed to suboptimal HD doses, ESA therapy, malnutrition-inflammation complex syndrome, and hyperparathyroidism.

We did not find any association between spKt/V and the presence of anemia or the changes in Hb, TSAT & serum ferritin. Nonetheless, the probability of suboptimal HD is still to be considered as all of our patients were receiving 9 HD-hours/week.

Erythropoiesis-stimulating agent therapy causes the bone marrow to strip iron off the circulating transferrin faster than it can replenish it from the iron stores [12]. We found no significant differences in ESA dose between anemic and non-anemic patients, nor any significant correlations between Hb levels and ESA doses, yet the calculated mean doses of ESAs might still be low. This issue is mainly related to financial and drug availability problems.

Like ours, nearly all the studies carried out on anemia in HD patients failed to find any significant association between the prevalence and severity of anemia and secondary hyperparathyroidism. All evidence of the role of PTH in renal anemia is indirect and based on the observation that parathyroidectomy in CKD patients is often followed by a rise in Hb level and a decrease in ESA dose [10].

Renal Association clinical practice guideline (2017) recommended Hb monitoring be performed prior to a mid-week HD session in HD patients receiving thrice weekly dialysis as this would minimize Hb variability due to over-hydration secondary to the longer inter-dialytic interval [13]. Unfortunately, sampling of our patients was not established prior to a mid-week HD session.

There are no available data addressing the treatment of anemic HD pediatric patients with low TSAT but high serum ferritin. We need to make sure that pediatric patients in this condition are administered optimum HD with ultrapure dialysis water, receive treatment for secondary hyperparathyroidism, are ensured proper nutrition with careful attention to micronutrients, and that other causes of anemia, especially missed hereditary conditions like β Thalassemia Minor, are excluded. We should also consider that serum ferritin represents only 1% of the total iron pool and behaves as an acute-phase reactant. The use of intravenous iron in anemic HD children with low TSAT but high ferritin needs to be studied in multicenter randomized controlled trials to assess its efficacy and safety. In the meantime, we can cautiously use intravenous iron on an individualized basis, weighing the risk–benefit and aiming to achieve TSAT of no more than 50% and a serum ferritin level no higher than 1000 ng/ml. In this case serum ferritin and TSAT assessment should be carried out every month. Extrapolating from the clinical practice guidelines used to evaluate iron overload in children with β-Thalassemia Major, assessment of hepatic and / or cardiac iron using MRI might be considered if serum ferritin is ≥ 1000 ng/ml [14]. Unfortunately, sampling of our patients was not established prior to a mid-week HD session and as such must be considered a limitation of the study. However, the results of this study give us a reason to conduct some research using more sensitive tools for monitoring anemia and iron status in such patients, like reticulocyte Hb content, percentage of hypochromic RBCs, soluble transferrin receptors, hepcidin, and hypoxia-inducible factor.