Comparison of oxidative stress markers after intravenous administration of iron dextran, sodium ferric gluconate, and iron sucrose in patients undergoing hemodialysis.
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.
Pai
Amy Barton
AB
College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131, USA. abpai@salud.unm.edu
Boyd
Alex V
AV
McQuade
Charles R
CR
Harford
Antonia
A
Norenberg
Jeffrey P
JP
Zager
Philip G
PG
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
D015415:Biomarkers; D005290:Ferric Compounds; D007505:Iron-Dextran Complex; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid; C035552:ferric gluconate