Comparison of Oxidative Stress Markers After Intravenous Administration of Iron Dextran, Sodium Ferric Gluconate, and Iron Sucrose in Patients Undergoing Hemodialysis

Study 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.

Design: Prospective, open-label, crossover study.

Setting: University-affiliated general clinical research center.

Patients: Twelve ambulatory patients undergoing hemodialysis.

Intervention: 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.

Measurements And Main 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).

Conclusion: 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.