Efficacy and Safety of Intravenous Iron Therapy for Functional Iron Deficiency Anemia in Hemodialysis Patients: A Meta-Analysis

Abstract

Background: Studies on benefits of intravenous iron therapy among hemodialysis patients with functional iron deficiency anemia have shown conflicting results. We conducted a meta-analysis to assess the efficacy and safety of intravenous iron in this subset of patients. Methods: We searched MEDLINE (through December 2012), the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov for single-arm studies and randomized controlled trials (RCT) that examined the effect of intravenous iron for functional iron deficiency anemia in hemodialysis patients on anemia parameters and markers of oxidative stress and inflammation. Studies of absolute iron deficiency were excluded. Random-effect model meta-analyses were used to compute changes in outcomes of interest. Results: We identified 34 studies (2,658 patients), representing 24 single-arm studies, and 10 parallel-arm RCT. In the analyses of the study arms, intravenous iron therapy resulted in a significant increase in hemoglobin, serum ferritin, transferrin saturation rate, serum iron, reticulocyte hemoglobin content as well as a significant decrease in the percentage of hypochromic erythrocytes and erythropoietin dose. There were significant increases in plasma malonyldialdehyde level and thiobarbituric acid-reactive substances, and a decrease in neutrophil respiratory burst. The analyses of the RCT revealed less robust net changes in these parameters, and there was no increased risk of adverse events including infections, cardiac events and mortality. Conclusions: Intravenous iron therapy for functional iron deficiency anemia in hemodialysis patients improves anemia parameters but exerts some effects on markers of oxidative stress that are of unclear clinical significance. The long-term safety and efficacy of this treatment strategy requires further study.

Considerations and Challenges in Defining Optimal Iron Utilization in Hemodialysis

“…[31][32][33] Trials have thus repeatedly shown oral iron to be ineffective at treating iron deficiency in the setting of hemodialysis, 34 which appears to be due to hepcidin-mediated blockade of iron absorption, ongoing iron losses, and poor patient tolerance. Consequently, guidelines have repeatedly recommended IVI in hemodialysis patients 13,14,23 -a recommendation consistent with trials demonstrating that administration of IVI increases hemoglobin and reduces ESA dose requirements, 22,35,36 although whether increasing hemoglobin or reducing ESA dose improves quality of life or reduces morbidity and mortality is unknown.…”

Intravenous Versus Oral Iron Supplementation for the Treatment of Anemia in CKD: An Updated Systematic Review and Meta-analysis

“…8 Compared to oral iron, IV iron better achieves a sustained hemoglobin (Hb) level response, which decreases the need for blood transfusions and improves quality of life (QoL) for many patients with CKD. [9][10][11] Concerns regarding IV iron therapy include anaphylaxis, bacterial infections, and atherosclerosis promotion. 12 However, a recent comprehensive meta-analysis, which included 103 trials and 14,434 patients, found that IV iron formulations were not associated with increased risk for serious adverse effects or with bacterial infections.…”

Blood conservation strategies and the management of perioperative anaemia

“…On the contrary, IVI was associated with an increased risk of infection (RR 1.33, 95% CI 1.10-1.64) [30]. These results are in contrast with another recent meta-analysis of IVI for the treatment of functional iron deficiency in dialysis patients, pooling data from 2658 patients from 34 studies, which also supported the effectiveness of IVI in increasing haemoglobin levels and improving serum iron indices, but demonstrated no increased risk of infection or other complications [31].…”

“…This can be done via cell recovery, which has been previously shown to reduce allogeneic transfusion rates by 38% (95% CI [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] and result in an average saving of 0.68 (95% CI 0.49-0.88) unit of RBC per patient, without negatively affecting clinical outcomes [51]. On the contrary, a recent randomized trial on 575 patients undergoing total knee and hip replacement indicated that the use of autologous blood transfusion drains had no effect on transfusion rates, given that all the patients were managed with a restrictive transfusion strategy, resulting in very low overall transfusion rates across both study arms [52].…”