Enhanced oxidative stress in haemodialysis patients receiving intravenous iron therapy

Iron balance is critical for adequate erythropoiesis and there remains much debate concerning the optimal timing and dosage of iron therapy for haemodialysis patients receiving recombinant human erythropoietin therapy.

In this study, we examined the influence of baseline ferritin level and intravenous infusion of 100 mg ferric saccharate on the oxidative status of the patients on maintenance haemodialysis. The levels of antioxidant enzymes and lipid peroxides were determined in erythrocytes and plasma of 50 uraemic patients on haemodialysis. These patients were divided into groups 1, 2, and 3, based on their baseline serum ferritin levels of <300, 301-600, and >601 microg/l, respectively.

We found that the mean superoxide dismutase (SOD) activities in the erythrocytes were similar in the three groups of patients and did not differ from those of the age-matched controls. On the other hand, all the haemodialysis patients showed significantly higher plasma SOD activity as compared to controls. After intravenous iron infusion, group 3 patients showed the largest decrease in plasma SOD activity. The plasma glutathione peroxidase (GSHPx) activities of the patients in all three groups and the erythrocyte GSHPx activities of the patients in the groups 2 and 3 were lower than those of the healthy controls. In all three groups of patients, no difference in GSHPx activity was found before and after intravenous iron infusion. On the other hand, we found that the average baseline levels of plasma lipid peroxides of all three groups of patients were significantly higher than that of the controls. The patients in group 3 with the highest serum ferritin levels showed the highest levels of plasma lipid peroxides. More importantly, we found that after iron infusion, the patients in all three groups, particularly those in group 3, showed significantly elevated levels of plasma lipid peroxides.

We demonstrated that increased oxidative stress in the blood circulation of the uraemic patients on haemodialysis is exacerbated by the elevated baseline serum ferritin levels and intravenous iron infusion. The resultant oxidative damage may contribute to the increased incidence of atherosclerosis in the patients with end-stage renal disease on long-term haemodialysis.