Impact of Intravenous Iron on Oxidative Stress and Mitochondrial Function in Experimental Chronic Kidney Disease

Nuhu, Faisal; Seymour, Anne-Marie; Bhandari, Sunil

doi:10.3390/antiox8100498

Cited by 23 publications

(25 citation statements)

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“…The glutathione system consisting of glutathione reductase, glutathione oxidase and glutathione, maintains the concentration of O 2 • and H 2 O 2 at physiological levels necessary for tissue repair and immune defence [ 3 ]. Therefore, the ratio of oxidised and reduced glutathione indicates the redox state of a cell and may represent a valuable tool for the assessment of oxidative stress and a target for drug-based antioxidant therapies [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Measurement of Glutathione as a Tool for Oxidative Stress Studies by High Performance Liquid Chromatography

et al. 2020

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Background: Maintenance of the ratio of glutathione in the reduced (GSH) and oxidised (GSSG) state in cells is important in redox control, signal transduction and gene regulation, factors that are altered in many diseases. The accurate and reliable determination of GSH and GSSG simultaneously is a useful tool for oxidative stress determination. Measurement is limited primarily to the underestimation of GSH and overestimation GSSG as a result of auto-oxidation of GSH. The aim of this study was to overcome this limitation and develop, optimise and validate a reverse-phase high performance liquid chromatographic (HPLC) assay of GSH and GSSG for the determination of oxidant status in cardiac and chronic kidney diseases. Methods: Fluorescence detection of the derivative, glutathione-O-pthaldialdehyde (OPA) adduct was used. The assay was validated by measuring the stability of glutathione and glutathione-OPA adduct under conditions that could affect the reproducibility including reaction time and temperature. Linearity, concentration range, limit of detection (LOD), limit of quantification (LOQ), recovery and extraction efficiency and selectivity of the method were assessed. Results: There was excellent linearity for GSH (r2 = 0.998) and GSSG (r2 = 0.996) over concentration ranges of 0.1 µM–4 mM and 0.2 µM–0.4 mM respectively. The extraction of GSH from tissues was consistent and precise. The limit of detection for GSH and GSSG were 0.34 µM and 0.26 µM respectively whilst their limits of quantification were 1.14 µM and 0.88 µM respectively. Conclusion: These data validate a method for the simultaneous measurement of GSH and GSSG in samples extracted from biological tissues and offer a simple determination of redox status in clinical samples.

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Section: Introductionmentioning

confidence: 99%

Measurement of Glutathione as a Tool for Oxidative Stress Studies by High Performance Liquid Chromatography

et al. 2020

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“…Nuhu et al [ 37 ] recently examined the mechanistic links between iron and CKD and concluded that the overall oxidation status in CKD is antioxidant. An interplay exists between iron homeostasis and oxidative stress in CKD that in turn impacts the effects of IV iron treatment [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

The comparative effects of intravenous iron on oxidative stress and inflammation in patients with chronic kidney disease and iron deficiency: a randomized controlled pilot study

Kassianides

Gordon

Sturmey

et al. 2021

Kidney Res Clin Pract

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Background: Concerns exist regarding the pro-oxidant and inflammatory potential of intravenous (IV) iron due to labile plasma iron (LPI) generation. This IRON-CKD trial compared the effects of different IV irons on oxidative stress and inflammation. Methods: In this randomized open-label explorative single-center study in the United Kingdom, non-dialysis-dependent chronic kidney disease (CKD) patients with iron deficiency were randomized (1:1:1:1) to receive a single infusion of 200 mg iron dextran, or 200 mg iron sucrose (IS), or 200 mg or 1,000 mg ferric derisomaltose (FDI) and were followed up for 3 months. The primary outcomes measured were induction of oxidative stress and inflammation. Secondarily, efficacy, vascular function, quality of life, and safety were monitored. Results: Forty patients were enrolled. No significant rise in oxidative stress existed, regardless of preparation or dose. There was a significant rise in LPI with 1,000 mg FDI at 2 hours that normalized within a week, not impacting oxidative stress or inflammation. A delayed rise in C-reactive protein was noted with IS. High-dose FDI produced a sustained serum ferritin increase (mean ± standard error of the mean of predose: 69.1 ± 18.4 μg/L, 3 months: 271.0 ± 83.3 μg/L; p = 0.007). Hemoglobin remained stable throughout. No adverse drug reactions were recorded during the study. Conclusion: A single dose of IV iron in CKD patients does not trigger oxidative stress or inflammation biomarkers. Third-generation IV irons have a reassuring safety profile, and high-dose FDI produced a sustained serum ferritin rise and more efficient iron repletion, with no significant pro-oxidant or inflammatory signals when compared to a lower dose and other IV irons.

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“…infusion may cause tissue damage via oxidative stress or increase susceptibility to infection. 31,70,71 Studies have both supported and refuted these concerns, with the balance of evidence suggesting that exposure to i.v. iron does not result in any greater risk of severe adverse reactions compared with oral iron or placebo.…”

Section: Iron Repletion and Adverse Eventsmentioning

confidence: 99%

“…iron does not result in any greater risk of severe adverse reactions compared with oral iron or placebo. 70…”

Section: Iron Repletion and Adverse Eventsmentioning

confidence: 99%

Treatment of Iron Deficiency Anemia in CKD and End-Stage Kidney Disease

Gutiérrez

2021

Kidney International Reports

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Iron deficiency is common in individuals with chronic kidney disease and plays a major role in the development of anemia. Oral and intravenous iron agents are both available to replete iron in patients with chronic kidney disease diagnosed with iron deficiency. The choice of which agent to use is most often dictated by goals of therapy, tolerability, convenience, and response to prior therapy. Diminished absorption of iron in the gastrointestinal tract and a high incidence of gastrointestinal adverse effects can reduce the efficacy of oral iron agents, necessitating the use of i.v. iron formulations to treat iron deficiency anemia, particularly in patients requiring kidney replacement therapy. Newer oral agents may help to overcome these limitations and help treat iron deficiency in those not requiring kidney replacement therapy. Recent studies have provided new evidence that more aggressive repletion of iron in patients with chronic kidney disease requiring kidney replacement therapy may provide benefits with respect to anemia management and hard clinical outcomes such as cardiovascular disease and survival.

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Impact of Intravenous Iron on Oxidative Stress and Mitochondrial Function in Experimental Chronic Kidney Disease

Cited by 23 publications

References 80 publications

Measurement of Glutathione as a Tool for Oxidative Stress Studies by High Performance Liquid Chromatography

Measurement of Glutathione as a Tool for Oxidative Stress Studies by High Performance Liquid Chromatography

The comparative effects of intravenous iron on oxidative stress and inflammation in patients with chronic kidney disease and iron deficiency: a randomized controlled pilot study

Treatment of Iron Deficiency Anemia in CKD and End-Stage Kidney Disease

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