scholarly journals Impact of intravenous iron on cardiac and skeletal oxidative stress and cardiac mitochondrial function in experimental uraemia chronic kidney disease

10.52586/4958 ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 442
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Mitochondrial Function ◽  
Intravenous Iron

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

Antioxidants ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 498 ◽  
Author(s):  
Faisal Nuhu ◽  
Anne-Marie Seymour ◽  
Sunil Bhandari
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Iron Deficiency ◽  
Glutathione Peroxidase ◽  
Mitochondrial Function ◽  
Iron Deficiency Anaemia ◽  
Deficiency Anaemia ◽  
Iv Iron

Background: Mitochondrial dysfunction is observed in chronic kidney disease (CKD). Iron deficiency anaemia (IDA), a common complication in CKD, is associated with poor clinical outcomes affecting mitochondrial function and exacerbating oxidative stress. Intravenous (iv) iron, that is used to treat anaemia, may lead to acute systemic oxidative stress. This study evaluated the impact of iv iron on mitochondrial function and oxidative stress. Methods: Uraemia was induced surgically in male Sprague-Dawley rats and studies were carried out 12 weeks later in two groups sham operated and uraemic (5/6 nephrectomy) rats not exposed to i.v. iron versus sham operated and uraemic rats with iv iron. Results: Induction of uraemia resulted in reduced iron availability (serum iron: 31.1 ± 1.8 versus 46.4 ± 1.4 µM), low total iron binding capacity (26.4 ± 0.7 versus 29.5 ± 0.8 µM), anaemia (haematocrit: 42.5 ± 3.0 versus 55.0 ± 3.0%), cardiac hypertrophy, reduced systemic glutathione peroxidase activity (1.12 ± 0.11 versus 1.48 ± 0.12 U/mL), tissue oxidative stress (oxidised glutathione: 0.50 ± 0.03 versus 0.36 ± 0.04 nmol/mg of tissue), renal mitochondrial dysfunction (proton/electron leak: 61.8 ± 8.0 versus 22.7 ± 5.77) and complex I respiration (134.6 ± 31.4 versus 267.6 ± 26.4 pmol/min/µg). Iron therapy had no effect on renal function and cardiac hypertrophy but improved anaemia and systemic glutathione peroxidase (GPx) activity. There was increased renal iron content and complex II and complex IV dysfunction. Conclusion: Iron therapy improved iron deficiency anaemia in CKD without significant impact on renal function or oxidant status.

Oxidative Stress and Inflammation in Chronic Kidney Disease: Role of Intravenous Iron and Vitamin D

2008 ◽  
Vol 21 (3) ◽  
pp. 214-224
Author(s):  
Amy Barton Pai ◽  
Todd A. Conner
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Vitamin D ◽  
Kidney Disease ◽  
Iron Supplementation ◽  
Intravenous Iron ◽  
Current Data ◽  
Vitamin D Analogs ◽  
Vitamin D Analog ◽  
Intravenous Iron Supplementation

Cardiovascular disease (CVD) is the leading cause of death among chronic kidney disease patients (CKD). The etiology of CVD in CKD is multifactorial and increasing evidence points to the important contribution of “nontraditional” risk factors including oxidative stress and inflammation. CKD is associated with a chronic imbalance of prooxidant and antioxidant factors that results in a state of chronic inflammation. Intravenous iron supplementation has been shown to induce oxidative stress and has been associated with lipid peroxidation and DNA damage. Conversely, treatment with vitamin D analogs has been associated with improved mortality in hemodialysis patients in 2 recent large cohort studies. These data suggest that vitamin D analogs may exert effects beyond their pharmacologic role in parathyroid hormone suppression. This article addresses the current data regarding the relative contributions of intravenous iron supplementation and vitamin D analog therapy on oxidative stress and inflammation in CKD patients.

scholarly journals Oxidative stress and renal injury with intravenous iron in patients with chronic kidney disease

2004 ◽  
Vol 65 (6) ◽  
pp. 2279-2289 ◽  
Author(s):  
Rajiv Agarwal ◽  
Nina Vasavada ◽  
Nadine G. Sachs ◽  
Shawn Chase
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Injury ◽  
Intravenous Iron

P0848PROSPECTIVE OPEN-LABEL EXPLORATIVE RANDOMISED SINGLE-CENTRE COMPARATIVE STUDY TO DETERMINE THE EFFECTS OF VARIOUS INTRAVENOUS IRON PREPARATIONS ON MARKERS OF OXIDATIVE STRESS AND KIDNEY INJURY IN CHRONIC KIDNEY DISEASE (IRON-CKD)

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Xenophon Kassianides ◽  
Ahmed Zeidan ◽  
Roger Sturmey ◽  
Andrew Gordon ◽  
Sunil Bhandari
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Endothelial Function ◽  
Intravenous Iron ◽  
Interleukin 10 ◽  
High Dose ◽  
Open Label ◽  
Iv Iron ◽  
Labile Iron

Abstract Background and Aims Iron deficiency is commonly treated with intravenous (IV) iron where oral iron is insufficient or cannot be tolerated. While IV iron is considered efficient and effective, safety concerns exist regarding the potential effect of IV iron on oxidative stress, inflammation and endothelial function. Transferrin is unable to saturate all the iron administered. Consequently, evidence has suggested differential generation of “free” or catalytic labile iron, depending on iron preparation. Labile iron stimulates lipid oxidation and free radical generation which can lead to increased oxidative stress, inflammation and endothelial dysfunction. The comparative risk of IV iron preparations has not been previ-ously extensively assessed. The possibility of IV iron leading to changes in oxidative stress, inflammation and endothelial function is assessed in this study. The potential interplay of IV iron changes with signaling pathways may lead to renal damage depending on the iron formulation used. This may lead to tubular and glomerular injury manifested as raised Neutrophil gelatinase-associated lipocalin (NGAL) levels in patients with chronic kidney disease (CKD). Method IRON-CKD is a prospective open-label explorative randomized, single-centre study assessing comparative safety and efficacy of three parenteral iron preparations. Patients with established CKD stages 3-5 and serum ferritin (SF) < 200microg/L and/or transferrin saturation (TS) <20% were recruited and randomized in a 1:1:1:1 ratio. The groups received a single infusion of 200mg Iron Dextran (Cosmofer ®), 200 mg Iron Sucrose (Venofer ®), and Iron Isomaltoside (Monofer ®) either as low (200mg) or high dose (1000mg). The patients were followed-up after IV iron at 2 hours and then at 1 day, 1 week, 1 month and 3 month intervals. Oxidative stress markers (Thiobarbituric acid reactive substances (TBARS)), inflammatory markers (Interleukin-1b, Interleukin-6, Interleukin-8, Interleukin-10) and surrogate markers of endothelial dysfunction (E-selectin, P-selectin) were measured. NGAL levels for establishment of potential acute kidney insult were measured. Free catalytic iron generation was also measured using the FeROS™ as-say. Data are presented as means and standard error of the mean (SEM). Statistical analysis was carried out using ANOVA. A p value of <0.05 was statistically significant. Results Forty patients were recruited and randomised with 10 per group. The mean age was 58.8 (±2.2) years and 23 (58%) were male. Free labile iron and TBARS increased within 2 hours of infusion (1.4 ΔFU/min (±0.5) to 7.4 ΔFU/min (±2.4)) (1083.0 nM (± 117.1) to 1552.6 nM (±156.0)) respectively with complete recovery within one week. TBARS and free labile iron were more pronounced within one day in the group receiving high dose Monofer® (TBARS: pre-infusion: 846.0 nM (±108.9) to 1865.0 nM (±203.2); Free labile iron: pre infusion: 0.3 ΔFU/min (±0.2) to 19.6 ΔFU/min (±7.1)). These were statistically significant with p < 0.001. These returned to pre-dosage levels and did not translate to any detriment in markers of inflammation or endothelial function (E-selectin or P-selectin). There was a non-statistically significant increase in Interleukin-10 (an anti-inflammatory cytokine) 2-hours post-infusion which was transient. Intravenous iron cumulatively and comparatively did not lead to a significant increase in NGAL (pre-infusion 570.5 ng/ml (±52.8); post-infusion 547.8 ng/ml (SEM: ±50.5); 3 months interval 534.8 ng/ml (±52.8)) at any given time point. Conclusion High dose of IV iron leads to a transient increased generation of free iron which disappears within one week. Iron therapy, at least in the short term, does not adversely affect markers of acute kidney injury, endothelial function, inflammation and oxidative stress status. This mechanistic data indicates that IV iron at both low and high doses is safe in patients with chronic kidney disease.

scholarly journals Protective Role of Histidine Supplementation Against Oxidative Stress Damage in the Management of Anemia of Chronic Kidney Disease

2018 ◽  
Vol 11 (4) ◽  
pp. 111 ◽  
Author(s):  
Mayra Vera-Aviles ◽  
Eleni Vantana ◽  
Emmy Kardinasari ◽  
Ngat Koh ◽  
Gladys Latunde-Dada
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Intravenous Iron ◽  
Protective Role ◽  
Health Condition ◽  
Divalent Metal Ions ◽  
Uremic Patients ◽  
Globin Synthesis ◽  
Stress Damage

Anemia is a major health condition associated with chronic kidney disease (CKD). A key underlying cause of this disorder is iron deficiency. Although intravenous iron treatment can be beneficial in correcting CKD-associated anemia, surplus iron can be detrimental and cause complications. Excessive generation of reactive oxygen species (ROS), particularly by mitochondria, leads to tissue oxidation and damage to DNA, proteins, and lipids. Oxidative stress increase in CKD has been further implicated in the pathogenesis of vascular calcification. Iron supplementation leads to the availability of excess free iron that is toxic and generates ROS that is linked, in turn, to inflammation, endothelial dysfunction, and cardiovascular disease. Histidine is indispensable to uremic patients because of the tendency toward negative plasma histidine levels. Histidine-deficient diets predispose healthy subjects to anemia and accentuate anemia in chronic uremic patients. Histidine is essential in globin synthesis and erythropoiesis and has also been implicated in the enhancement of iron absorption from human diets. Studies have found that L-histidine exhibits antioxidant capabilities, such as scavenging free radicals and chelating divalent metal ions, hence the advocacy for its use in improving oxidative stress in CKD. The current review advances and discusses evidence for iron-induced toxicity in CKD and the mechanisms by which histidine exerts cytoprotective functions.

scholarly journals Oxidative Stress in Non-Dialysis-Dependent Chronic Kidney Disease Patients

2021 ◽  
Vol 18 (15) ◽  
pp. 7806
Author(s):  
Patricia Tomás-Simó ◽  
Luis D’Marco ◽  
María Romero-Parra ◽  
Mari Carmen Tormos-Muñoz ◽  
Guillermo Sáez ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Reduced Glutathione ◽  
Genetic Material ◽  
Future Research ◽  
Control Group ◽  
Dialysis Patients ◽  
Early Stages ◽  
Molecular Lines

Background: Cardiovascular complications are the leading cause of morbidity and mortality at any stage of chronic kidney disease (CKD). Moreover, the high rate of cardiovascular mortality observed in these patients is associated with an accelerated atherosclerosis process that likely starts at the early stages of CKD. Thus, traditional and non-traditional or uremic-related factors represent a link between CKD and cardiovascular risk. Among non-conventional risk factors, particular focus has been placed on anaemia, mineral and bone disorders, inflammation, malnutrition and oxidative stress and, in this regard, connections have been reported between oxidative stress and cardiovascular disease in dialysis patients. Methods: We evaluated the oxidation process in different molecular lines (proteins, lipids and genetic material) in 155 non-dialysis patients at different stages of CKD and 45 healthy controls. To assess oxidative stress status, we analyzed oxidized glutathione (GSSG), reduced glutathione (GSH) and the oxidized/reduced glutathione ratio (GSSG/GSH) and other oxidation indicators, including malondialdehyde (MDA) and 8-oxo-2’-deoxyguanosine (8-oxo-dG). Results: An active grade of oxidative stress was found from the early stages of CKD onwards, which affected all of the molecular lines studied. We observed a heightened oxidative state (indicated by a higher level of oxidized molecules together with decreased levels of antioxidant molecules) as kidney function declined. Furthermore, oxidative stress-related alterations were significantly greater in CKD patients than in the control group. Conclusions: CKD patients exhibit significantly higher oxidative stress than healthy individuals, and these alterations intensify as eGFR declines, showing significant differences between CKD stages. Thus, future research is warranted to provide clearer results in this area.

scholarly journals Oxidative stress increases 1-deoxysphingolipid levels in chronic kidney disease

2021 ◽  
Vol 164 ◽  
pp. 139-148
Author(s):  
Ting Gui ◽  
Yunlun Li ◽  
Shijun Zhang ◽  
Irina Alecu ◽  
Qingfa Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease

scholarly journals Indoxyl-Sulfate-Induced Redox Imbalance in Chronic Kidney Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 936
Author(s):  
Chien-Lin Lu ◽  
Cai-Mei Zheng ◽  
Kuo-Cheng Lu ◽  
Min-Tser Liao ◽  
Kun-Lin Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Muscle Wasting ◽  
Mesangial Cells ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Indoxyl Sulfate ◽  
Uremic Toxin ◽  
Tubulointerstitial Injury

The accumulation of the uremic toxin indoxyl sulfate (IS) induces target organ damage in chronic kidney disease (CKD) patients, and causes complications including cardiovascular diseases, renal osteodystrophy, muscle wasting, and anemia. IS stimulates reactive oxygen species (ROS) production in CKD, which impairs glomerular filtration by a direct cytotoxic effect on the mesangial cells. IS further reduces antioxidant capacity in renal proximal tubular cells and contributes to tubulointerstitial injury. IS-induced ROS formation triggers the switching of vascular smooth muscular cells to the osteoblastic phenotype, which induces cardiovascular risk. Low-turnover bone disease seen in early CKD relies on the inhibitory effects of IS on osteoblast viability and differentiation, and osteoblastic signaling via the parathyroid hormone. Excessive ROS and inflammatory cytokine releases caused by IS directly inhibit myocyte growth in muscle wasting via myokines’ effects. Moreover, IS triggers eryptosis via ROS-mediated oxidative stress, and elevates hepcidin levels in order to prevent iron flux in circulation in renal anemia. Thus, IS-induced oxidative stress underlies the mechanisms in CKD-related complications. This review summarizes the underlying mechanisms of how IS mediates oxidative stress in the pathogenesis of CKD’s complications. Furthermore, we also discuss the potential role of oral AST-120 in attenuating IS-mediated oxidative stress after gastrointestinal adsorption of the IS precursor indole.

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