Iron-induced oxidative stress in haemodialysis patients: a pilot study on the impact of diabetes

Campenhout, Ann Van; Campenhout, Christel Van; Lagrou, A.; Manuel-y-Keenoy, Begoña

doi:10.1007/s10534-007-9104-9

Cited by 19 publications

(16 citation statements)

References 45 publications

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“…In the clinic, however, we were surprised by a small number of HHT patients who spontaneously volunteered that they could not use iron tablets or infusions to treat their iron deficiency because the iron treatments precipitated nosebleeds within hours. This prompted us to examine whether endothelial cells were modified by iron concentrations similar to those present in the bloodstream after iron tablets or infusions . Previous studies demonstrated toxicity at much higher iron concentrations, relevant to iron overload disorders or experimental endothelial models .…”

Section: Introductionmentioning

confidence: 99%

Can Iron Treatments Aggravate Epistaxis in Some Patients With Hereditary Hemorrhagic Telangiectasia?

et al. 2016

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Objectives/HypothesisTo examine whether there is a rationale for iron treatments precipitating nosebleeds (epistaxis) in a subgroup of patients with hereditary hemorrhagic telangiectasia (HHT).Study DesignSurvey evaluation of HHT patients, and a randomized control trial in healthy volunteers.MethodsNosebleed severity in response to iron treatments and standard investigations were evaluated by unbiased surveys in patients with HHT. Serial blood samples from a randomized controlled trial of 18 healthy volunteers were used to examine responses to a single iron tablet (ferrous sulfate, 200 mg).ResultsIron tablet users were more likely to have daily nosebleeds than non–iron‐users as adults, but there was no difference in the proportions reporting childhood or trauma‐induced nosebleeds. Although iron and blood transfusions were commonly reported to improve nosebleeds, 35 of 732 (4.8%) iron tablet users, in addition to 17 of 261 (6.5%) iron infusion users, reported that their nosebleeds were exacerbated by the respective treatments. These rates were significantly higher than those reported for control investigations. Serum iron rose sharply in four of the volunteers ingesting ferrous sulfate (by 19.3–33.1 μmol/L in 2 hours), but not in 12 dietary controls (2‐hour iron increment ranged from −2.2 to +5.0 μmol/L). High iron absorbers demonstrated greater increments in serum ferritin at 48 hours, but transient rises in circulating endothelial cells, an accepted marker of endothelial damage.ConclusionsIron supplementation is essential to treat or prevent iron deficiency, particularly in patients with pathological hemorrhagic iron losses. However, in a small subgroup of individuals, rapid changes in serum iron may provoke endothelial changes and hemorrhage.Level of Evidence4. Laryngoscope, 126:2468–2474, 2016

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Section: Introductionmentioning

confidence: 99%

Can Iron Treatments Aggravate Epistaxis in Some Patients With Hereditary Hemorrhagic Telangiectasia?

et al. 2016

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“…However, all IV iron products have the potential to have direct release of iron [non-transferrin bound iron (NTBI)] into plasma, a physicochemical characteristic that appears to be directly related to molecular weight, and drug clearance by the RES (Danielson 2004;Pai et al 2010;Balakrishnan et al 2009;Van Wyck et al 2004). Single and multi-dose studies of IV iron have demonstrated significant increases in biomarkers of oxidative stress in HD patients indicating that IV iron can induce lipid peroxidation, DNA damage and increase inflammatory mediators (Van Campenhout et al 2008;Kuo et al 2008;Garcia-Fernandez et al 2010). A comparative analysis of commercially available preparations has shown that in vitro that iron sucrose, sodium ferric gluconate and iron dextran induce oxidative stress but higher rates of cell death were apparent among iron sucrose, sodium ferric gluconate treated human proximal tubule cells (Zager et al 2002).…”

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confidence: 99%

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

Pai

Conner²,

McQuade

et al. 2011

Biometals

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

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“…Therefore, it is general recommendation not to use single IV bolus doses >100 mg. In vivo data on oversaturation have been published in humans after injection of 100 mg IS [12,23,44,45], and 62.5–125 mg iron-gluconate (IG) [25,46] and ID [47]. Once again, the interpretation of these data on oversaturation can be troublesome because of the possibility of direct assay interference with the IV iron agent.…”

Section: Discussionmentioning

confidence: 99%

Acute Oxidative Stress following Intravenous Iron Injection in Patients on Chronic Hemodialysis: A Comparison of Iron-Sucrose and Iron-Dextran

2010

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Background/Aims: Intravascular iron release from parenteral iron formulations can catalyze various harmful oxidative reactions. These topics have mainly been investigated in vivo with iron-sucrose (IS). The aim of our study was to compare IS and iron-dextran (ID) regarding iron release and induction of oxidative stress. Methods: Twenty hemodialysis patients were enrolled. Plasma iron and oxidative stress parameters were measured before and 10 min after intravenous (IV) injection of 100 mg IS and ID, respectively. Results: Intravascular iron increased significantly more after IS. The mean ± SD changes in plasma iron were 314 ± 172% after IS versus 90 ± 44% after ID (p < 0.001). Comparable changes in non-transferrin bound iron were 86 ± 42 versus 45 ± 45%, respectively (p < 0.05). Plasma ascorbic free radical did not change following ID (–1.8 ± 11.2%) but increased by 29 ± 31.3% after IS (p < 0.01). Further, protein carbonyls increased following IS (p < 0.05) but not after ID. Conclusion: Increased oxidative stress was found only after IV injection with IS.

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Iron-induced oxidative stress in haemodialysis patients: a pilot study on the impact of diabetes

Abstract: In haemodialysis patients, higher lipid peroxidation is determined by higher body iron stores. The increase induced by iron infusion is accompanied by a loss in iron-binding antioxidant capacity and is more pronounced in diabetes mellitus.

Cited by 19 publications

References 45 publications

Can Iron Treatments Aggravate Epistaxis in Some Patients With Hereditary Hemorrhagic Telangiectasia?

Can Iron Treatments Aggravate Epistaxis in Some Patients With Hereditary Hemorrhagic Telangiectasia?

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

Acute Oxidative Stress following Intravenous Iron Injection in Patients on Chronic Hemodialysis: A Comparison of Iron-Sucrose and Iron-Dextran

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