Analysis of potential iron toxicity in hemodialysis patients under intravenous iron treatment

Background: The use of higher doses of iron for the treatment of anemia in hemodialysis patients allows lower doses of erythropoiesis-stimulating agents; however, there are concerns regarding the risk of iron toxicity. This study aimed to evaluate the potential toxicity of iron deposition in prevalent hemodialysis patients on iron therapy and its relationship with parameters used to assess iron status, plasma protein oxidation, and cellular iron toxicity. Methods: Magnetic resonance imaging was performed in 56 patients to assess hepatic iron deposition, which was related to clinical and analytical parameters. In patients included in the first and fourth quartiles according to hepatic iron deposition, plasma protein oxidative stress was quantified, as well as iron and cytokine levels in peripheral blood mononuclear cells (PBMCs). Results: Patients with higher hepatic iron deposition had a longer time on hemodialysis (41.0±44.9 vs 4.9±3.4 months, p<0.001) and higher ferritin levels (1181±532 vs 429±278 ng/ml, p<0.001) than those with lower hepatic iron deposition, without differences in transferrin saturation or hepatic enzyme serum concentration. No differences were found in plasma protein oxidation, iron content, or cytokine mRNA content in PBMCs, except for a decrease in IL-6 levels in patients with higher hepatic iron deposition. Conclusions: Patients with longer hemodialysis times had higher iron stores, suggesting that iron treatment over time increases hepatic iron deposition. No parameters supporting increased toxicity in patients with higher hepatic iron deposition were observed; therefore, more proactive treatment with intravenous iron to improve anemia management may not necessarily induce deleterious effects in hemodialysis patients.