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      Effect of methoxy polyethylene glycol-epoetin beta on oxidative stress in predialysis patients with chronic kidney disease

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          Abstract

          Background

          There is data in the literature indicating increased oxidative stress in chronic kidney disease (CKD). Erythropoiesis-stimulating agents (ESAs), which are commonly used to treat anemia in patients with CKD, seem to have an antioxidant action, which could be a part of nephroprotection. The aim of the current study was to investigate the effect of a long half-life ESA, methoxy polyethylene glycol-epoetin beta (Mircera), on some markers of oxidative stress in predialysis patients with CKD.

          Material/Methods

          Peripheral blood was collected from 28 predialysis CKD patients 2 times, before Mircera treatment and after achieving target hemoglobin (Hb), and 15 healthy subjects (control group). Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activity in erythrocytes were measured according to commonly used methods as a function of the antioxidant defense system. To assess reactive oxygen species (ROS) production, malondialdehyde (MDA) concentration in erythrocytes and in plasma was measured according to a commonly used method.

          Results

          SOD, GSH-Px, and CAT activity were similar, but plasma and erythrocyte MDA concentrations were significantly higher in CKD patients before ESA treatment in comparison to the control group. SOD, GSH-Px, and CAT activity was significantly higher, but plasma and erythrocyte MDA concentrations were significantly lower, in CKD patients after ESA treatment in comparison to these patients before treatment. We did not find a significant correlation between Hb concentration and SOD, GSH-Px, and CAT activity and plasma, as well as erythrocyte MDA concentrations. Analysis of all investigated groups showed a significant negative correlation between Hb concentration and plasma MDA concentration.

          Conclusions

          Our results suggest that treatment of anemia with methoxy polyethylene glycol-epoetin beta may inhibit oxidative stress in predialysis patients with CKD by enhancing the antioxidant defense system and reducing ROS production.

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          Most cited references57

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          A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase.

          R. F. Beers, I. Sizer (1952)
          Article 0 comments Cited 652 times – based on 0 reviews     Review now
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            Oxidative stress in uremia: nature, mechanisms, and potential consequences.

            Nosratola D. Vaziri (2004)
            Oxidative stress has emerged as a constant feature of chronic renal failure (CRF). The presence of oxidative stress in CRF is evidenced by an overabundance of lipid, carbohydrate, and protein oxidation products in the plasma and tissues of uremic patients and animals. We recently have shown that oxidative stress in CRF animals is associated with and, in part, owing to up-regulation of superoxide-producing enzyme, nicotinamide-adenine dinucleotide phosphate (NAD(P)H) oxidase, and down-regulation of superoxide dismutase (SOD). The functional significance of these findings was confirmed by favorable response to administration of the cell-permeable SOD-mimetic agent, tempol, in CRF rats. Oxidative stress in CRF plays an important role in the pathogenesis of the associated hypertension (oxidation of NO and arachidonic acid and vascular remodeling), cardiovascular disease (oxidation of lipoproteins, atherogenesis), neurologic disorders (nitration of brain proteins, oxidation of myelin), anemia (reduction of erythrocyte lifespan), inflammation (nuclear factor kappa B activation), fibrosis, apoptosis, and accelerated aging. The CRF-induced oxidative stress is aggravated by diabetes, uncontrolled hypertension, and autoimmune diseases, which independently increase production of reactive oxygen intermediates, and frequently are associated with CRF. In addition, dialysis treatment (blood interaction with dialyzer membrane and dialysate impurities), acute and chronic infections (blood access infection, hepatitis, and so forth), and excessive parenteral iron administration intensify CRF-associated oxidative stress and its adverse consequences in patients with end-stage renal disease. The problem is compounded by limited intake of fresh fruits and vegetables (K(+) restriction), which contain numerous natural phytochemicals and antioxidant vitamins.
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              The determinants of endothelial dysfunction in CKD: oxidative stress and asymmetric dimethylarginine.

              Kayser Cağlar, Abdulgaffar Vural, Gultekin Genctoy … (2005)
              Oxidative stress is related to endothelial dysfunction (ED) and cardiovascular outcomes in patients with chronic kidney disease. Increased asymmetric dimethylarginine (ADMA) levels are among the main causes of ED. We aim to investigate any association between ED and ADMA levels, as well as levels of oxidative stress markers, in patients with chronic kidney disease. One hundred fifty-nine patients without diabetes with chronic kidney disease were studied. Staging was performed according to glomerular filtration rate, determined as stages 1 to 5 according to the Kidney Disease Outcomes Quality Initiative (n = 30, 33, 28, 32, and 36, respectively). The control group consisted of 30 healthy subjects. Oxidative stress markers (plasma malondialdehyde [MDA], erythrocyte superoxide dismutase [SOD], glutathione peroxidase [GSH-Px]), trace elements (erythrocyte zinc [EZn], erythrocyte copper [ECu]), plasma selenium (Se), and serum ADMA were studied. Brachial artery endothelium-dependent vasodilatation (FMD) was calculated for all. FMD, SOD, GSH-Px, EZn, ECu, and Se values were lower, whereas MDA and ADMA levels were higher in patients than controls. Glomerular filtration rate correlated negatively with MDA and ADMA levels and positively with FMD, SOD, and GSH-Px values. These parameters were significantly different among patients with stages 2, 3, 4, and 5 (hemodialysis group; P < 0.001 for all). Regression analysis showed that ADMA (beta = -0.228; P < 0.01), SOD (beta = 0.405; P < 0.001), and oxidized low-density lipoprotein levels (beta = -0.428; P < 0.001) were related independently to FMD, whereas glomerular filtration rate was not involved in the model. The present results imply that FMD, oxidative stress, and ADMA levels all are associated with stage of chronic kidney disease. Additionally, levels of oxidative stress markers and ADMA independently determine endothelial function.
              Article 0 comments Cited 92 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Med Sci Monit
                Journal ID (iso-abbrev): Med. Sci. Monit
                Journal ID (publisher-id): Medical Science Monitor
                Title: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research
                Publisher: International Scientific Literature, Inc.
                ISSN (Print): 1234-1010
                ISSN (Electronic): 1643-3750
                Publication date Collection: 2013
                Publication date (Electronic): 08 November 2013
                Volume: 19
                Pages: 954-959
                Affiliations
                [1 ]Department of Nephrology, Hypertension and Family Medicine, Medical University, ŁódŸ, Poland
                [2 ]Department of Physiology, Medical University, ŁódŸ, Poland
                [3 ]Department of Hypertension, Medical University, ŁódŸ, Poland
                Author notes
                Corresponding Author: Jacek Rysz, e-mail: jacek.rysz@ 123456skwam.lodz.pl
                [A]

                Study Design

                [B]

                Data Collection

                [C]

                Statistical Analysis

                [D]

                Data Interpretation

                [E]

                Manuscript Preparation

                [F]

                Literature Search

                [G]

                Funds Collection

                Article
                Publisher ID: 884024
                DOI: 10.12659/MSM.884024
                PMC ID: 3829740
                PubMed ID: 24201565
                SO-VID: e527694a-6e12-4b6a-8468-f557c743c7ab
                Copyright © © Med Sci Monit, 2013
                License:

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License

                History
                Date received : 28 November 2012
                Date accepted : 27 March 2013
                Categories
                Subject: Clinical Research

                Keywords: chronic kidney disease (ckd),erythropoiesis-stimulating agents,oxidative stress,anemia
                Data availability:
                Keywords: chronic kidney disease (ckd), erythropoiesis-stimulating agents, oxidative stress, anemia

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