High ferritin is associated with liver and bone marrow iron accumulation: Effects of 1-year deferoxamine treatment in hemodialysis-associated iron overload

PLoS One. 2024 Aug 9;19(8):e0306255. doi: 10.1371/journal.pone.0306255. eCollection 2024.

Abstract

Background: Iron (Fe) supplementation is a critical component of anemia therapy for patients with chronic kidney disease (CKD). However, serum Fe, ferritin, and transferrin saturation, used to guide Fe replacement, are far from optimal, as they can be influenced by malnutrition and inflammation. Currently, there is a trend of increasing Fe supplementation to target high ferritin levels, although the long-term risk has been overlooked.

Methods: We prospectively enrolled 28 patients with CKD on hemodialysis with high serum ferritin (> 1000 ng/ml) and tested the effects of 1-year deferoxamine treatment, accompanied by withdrawal of Fe administration, on laboratory parameters (Fe status, inflammatory and CKD-MBD markers), heart, liver, and iliac crest Fe deposition (quantitative magnetic resonance imaging [MRI]), and bone biopsy (histomorphometry and counting of the number of Fe positive cells in the bone marrow).

Results: MRI parameters showed that none of the patients had heart iron overload, but they all presented iron overload in the liver and bone marrow, which was confirmed by bone histology. After therapy, ferritin levels decreased, although neither hemoglobin levels nor erythropoietin dose was changed. A significant decrease in hepcidin and FGF-23 levels was observed. Fe accumulation was improved in the liver and bone marrow, reaching normal values only in the bone marrow. No significant changes in turnover, mineralization or volume were observed.

Conclusions: Our data suggest that treatment with deferoxamine was safe and could improve Fe accumulation, as measured by MRI and histomorphometry. Whether MRI is considered a standard tool for investigating bone marrow Fe accumulation requires further investigation. Registry and the registration number of clinical trial: ReBEC (Registro Brasileiro de Ensaios Clinicos) under the identification RBR-3rnskcj available at: https://ensaiosclinicos.gov.br/pesquisador.

MeSH terms

  • Aged
  • Bone Marrow* / drug effects
  • Bone Marrow* / metabolism
  • Bone Marrow* / pathology
  • Deferoxamine* / administration & dosage
  • Deferoxamine* / therapeutic use
  • Female
  • Ferritins* / blood
  • Ferritins* / metabolism
  • Fibroblast Growth Factor-23
  • Hepcidins / metabolism
  • Humans
  • Iron Overload* / drug therapy
  • Iron Overload* / etiology
  • Iron Overload* / metabolism
  • Iron* / metabolism
  • Liver* / diagnostic imaging
  • Liver* / drug effects
  • Liver* / metabolism
  • Liver* / pathology
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Prospective Studies
  • Renal Dialysis*
  • Renal Insufficiency, Chronic / blood
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / drug therapy
  • Renal Insufficiency, Chronic / metabolism
  • Renal Insufficiency, Chronic / therapy

Substances

  • Ferritins
  • Deferoxamine
  • Iron
  • Fibroblast Growth Factor-23
  • Hepcidins

Grants and funding

This work was supported by the Brazilian National Council for Scientific and Technological Development (CNPq; grant number 434758/2018-3). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.