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

Abstract

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.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

The author(s) received no specific funding for this work.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The Ethics Committee of the Hospital Universitario Príncipe de Asturias, considered issuing a favorable opinion for the study to be carried out.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data Availability

All relevant data are within the manuscript and n Supporting Information files.

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