Non-transferrin bound iron, cytokine activation and intracellular reactive oxygen species generation in hemodialysis patients receiving intravenous iron dextran or iron sucrose

摘要: Intravenous (IV) iron supplementation is widely used to support erythropoeisis in hemodialysis patients. IV products are associated with oxidative stress that has been measured principally by circulating biomarkers such as of lipid peroxidation. The pro-oxidant effects presumed be due at least part, free or non-transferrin bound (NTBI). However, the on intracellular redox status and downstream effectors not known. This prospective, crossover study compared cytokine activation, reactive oxygen species generation after single doses sucrose dextran. was a open-label, study. Ten patients end-stage renal disease (ESRD) four age sex-matched healthy were assigned receive 100 mg each product over 5 min random sequence 2 week washout between products. Subjects fasted fed low diet General Clinical Research Center University New Mexico. Serum plasma samples for IL-1, IL-6, TNF-α IL-10 NTBI obtained baseline, 60 240 infusion. Peripheral blood mononuclear cells (PBMC) isolated same time points stained fluorescent probes identify mitochondrial membrane potential (Δψm) flow cytometry. Lipid peroxidation assessed F2 isoprostane concentration. Mean ± SEM maximum serum values significantly higher among receiving IS ID (2.59 0.31 1.0 0.36 µM, respectively, P = 0.005 vs. ID) area under concentration–time curve (AUC) 3-fold versus (202 53 74 23 µM*min/l, 0.04) ESRD patients, indicating increased exposure NTBI. administration pro-inflammatory cytokines. IL-6 concentrations most profoundly, 2.6 2.1 fold increase from baseline given ID, respectively (P < 0.05 baseline). In controls, undetectable administration. Most had ROS generation, however, there no difference IS. Only one control post iron. All controls experienced loss Δψm (100% 50% ID). also nadir min. both compounds produced similar activation more pronounced effect iron-induced production pivotal signaling pathways needs explored.