Increase in plasma esterified F-2-isoprostanes following intravenous iron infusion in patients on hemodialysis

Background. In epoetin-treated dialysis patients. currently iron is adminis tered by the intravenous route to maintain optimum erythropoiesis. However, rapid infusion of iron in excess of transferrin binding capacity can lead to the availability of unbound iron that can theoretically catalyze peroxid ation of lipids, such as low-density lipoprotein (LDL), which when oxidativ ely modified is proinflammatory and promotes atherogenesis. Methods. To address this issue, our study used one of the most specific mea sures of lipid peroxidation available, namely gas chromatography/mass spect ometry (GC/MS) analysis of F-2-isoprostanes. Using a prospective design, bl ood samples were collected 15 minutes before (pre) and 30 minutes after (po st) a one-hour infusion of 700 mg bolus of intravenous iron in 22 adult hom e-hemodialysis patients on a non-hemodialysis day. Results. With iron-dextran infusion, serum iron markedly increased (mean +/ - SE, 42 +/- 4 vs. 311 +/- 92 mug/dL, P < 0.0001) and exceeded the transfer rin saturation of 100% in 22 out of 22 patients (pre 23 +/- 3 vs. post 165 +/- 8%, P < 0.0001). Plasma concentrations of free F-2-isoprostanes did not change significantly following infusion of iron (pre 40 +/- 5 vs. post 39 +/- 6 pg/mL). However, levels of F-2-isoprostanes esterified in plasma lipo proteins increased significantly in the postinfusion samples (pre 199 +/- 1 9 vs. post 233 = 25 pg/mL. P < 0.004). Pre-infusion levels of serum iron co rrelated directly with pre-infusion levels of esterified F-2-isoprostanes ( r = 0.56, P = 0.008), which persisted in the postinfusion period (r = 0.43, P = 0.04). However, there was no correlation between esterified F-2-isopro stanes and serum ferritin levels. In the last four patients in whom blood s amples were collected five hours after the intravenous iron infusion. there were further increases in esterified F-2-isoprostanes that very closely co rrelated with postinfusion serum iron levels (r = 0.99 P = 0.013). In a con trol study, the in vitro addition of iron dextran to blood samples did not increase free or esterified F-2-isoprostanes, suggesting that the increase in esterified F-2-isoprostanes seen in vivo after iron infusion in patients is not due to a procedural artifact. Conclusion. Collectively our data suggest that high levels of serum iron ap pearing soon after a large bolus of iron infusion is associated with signif icant, albeit modest, increases in levels of F-2-isoprostanes esterified in plasma lipoproteins that tended to increase with time. Although it is unce rtain whether this degree of lipid peroxidation may have deleterious effect s, it may be sagacious to explore whether this can be prevented by slow inf usion of frequent smaller doses of iron and, if necessary, along with admin istration of antioxidants.