title: Comparison of oxidative stress markers after intravenous administration of iron dextran, sodium ferric gluconate, and iron sucrose in patients undergoing hemodialysis.
abstract: OBJECTIVE
  To compare non-transferrin-bound iron and markers of oxidative stress after single intravenous doses of iron dextran, sodium ferric gluconate, and iron sucrose.
  
  
  METHODS
  Prospective, open-label, crossover study.
  
  
  METHODS
  University-affiliated general clinical research center.
  
  
  METHODS
  Twelve ambulatory patients undergoing hemodialysis.
  
  
  METHODS
  Patients received 100 mg of intravenous iron dextran, sodium ferric gluconate, and iron sucrose in random sequence, with a 2-week washout period between treatments.
  
  
  RESULTS
  Serum samples for transferrin saturation, non-transferrin-bound iron, and malondialdehyde (MDA; marker of lipid peroxidation) were obtained before (baseline) and 30, 60, 120, and 360 minutes and 2 weeks after each iron infusion. A serum sample for hemeoxygenase-1 (HO-1) RNA was obtained at baseline and 360 minutes after infusion. Non-transferrin-bound iron values were significantly higher 30 minutes after administration of sodium ferric gluconate and iron sucrose compared with iron dextran (mean +/- SEM 10.1 +/- 2.2, 3.8 +/- 0.8, and 0.23 +/-0.1 microM, respectively, p<0.001 for sodium ferric gluconate vs iron dextran, p = 0.002 for iron sucrose vs iron dextran). A significant positive correlation was noted between transferrin saturation and the presence of non-transferrin-bound iron for sodium ferric gluconate and iron sucrose (r2 = 0.37 and 0.45, respectively, p<0.001) but not for iron dextran (r2 = 0.09). After sodium ferric gluconate, significantly more samples showed increases in MDA levels from baseline compared with iron sucrose and iron dextran (p = 0.006); these increased levels were associated with the presence of non-transferrin-bound iron, baseline transferrin saturation above 30%, baseline transferrin levels below 180 mg/dl, and ferritin levels above 500 ng/ml (p<0.05). However, only a transferrin level below 180 mg/dl was independently associated (odds ratio 4.8, 95% confidence interval 1.2-15.3).
  
  
  CONCLUSIONS
  Iron sucrose and sodium ferric gluconate were associated with greater non-transferrin-bound iron appearance compared with iron dextran. However, only sodium ferric gluconate showed significant increases in lipid peroxidation. The relationship between non-transferrin-bound iron from intravenous iron and oxidative stress warrants further exploration.
authors.affiliation: College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131, USA. abpai@salud.unm.edu
authors.forename: Amy Barton
authors.initials: AB
authors.lastname: Pai
authors.forename: Alex V
authors.initials: AV
authors.lastname: Boyd
authors.forename: Charles R
authors.initials: CR
authors.lastname: McQuade
authors.forename: Antonia
authors.initials: A
authors.lastname: Harford
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Norenberg
authors.forename: Philip G
authors.initials: PG
authors.lastname: Zager
mesh_terms: D015415:Biomarkers; D018592:Cross-Over Studies; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid; D006801:Humans; D007262:Infusions, Intravenous; D007505:Iron-Dextran Complex / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D011446:Prospective Studies; D006435:Renal Dialysis
chemical_list: D015415:Biomarkers; D005290:Ferric Compounds; D007505:Iron-Dextran Complex; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid; C035552:ferric gluconate