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      Serum Concentrations of F 2-Isoprostanes and 4-Hydroxynonenal in Hemodialysis Patients in Relation to Inflammation and Renal Anemia

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          Abstract

          Background

          Patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD) are apparently exposed to enhanced oxidative stress and to inflammation. It was the aim of this study to characterize the state of systemic oxidative stress of ESRD patients before and following HD using highly specific biomarkers, F 2-isoprostanes and 4-hydroxynonenal (HNE). Furthermore the question should be answered, if there are associations between inflammation and systemic oxidative stress and/or between systemic oxidative stress and renal anemia, which is more or less typical for HD patients.

          Patients and methods

          Concentrations of F 2-isoprostanes, HNE, C-reactive protein (CRP) as marker of inflammation, and hemoglobin were measured in serum samples of patients with ESRD before and after HD and of healthy control persons for comparison. Total (esterified plus free) F 2-isoprostanes were quantified by highly sensitive gas chromatography/mass spectrometry technique, HNE by thin layer chromatography and HPLC/UV detection, CRP by immunoturbidimetry and hemoglobin by clinico-chemical routine assay.

          Results

          1. HD patients showed significantly higher serum concentrations of F 2-isoprostanes and HNE than healthy human control subjects. 2. Total (esterified plus free) F 2-isoprostane levels before HD were not significantly different from those after HD, whereas HNE levels were significantly decreased in patients after HD. 3. F 2-isoprostane concentrations in HD patients correlated with the levels of CRP, whereas HNE concentrations inversely correlated with the content of hemoglobin.

          Conclusion

          Both, F 2-isoprostanes and HNE serum concentrations are useful oxidative stress parameters in ESRD patients undergoing HD. Whereas HNE strongly correlates with the severity of renal anemia, leading to left heart insufficiency, F 2-isoprostanes (sum of free plus esterified) highly correlate with the degree of inflammation.

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          Isoprostanes: markers and mediators of oxidative stress.

          Peter Barnes, Paolo Montuschi, Beverly L. Roberts (2004)
          Some years ago it was discovered that prostaglandin F2-like compounds are formed in vivo by nonenzymatic free radical-catalyzed peroxidation of arachidonic acid. Because these compounds are a series of isomers that contain the prostane ring of prostaglandins, they were termed F2-isoprostanes. Intermediates in the isoprostane pathway are prostaglandin H2-like compounds that become reduced to form F2-isoprostanes but also undergo rearrangement in vivo to form E2-, D2-, A2-, J2-isoprostanes, isothromboxanes, and highly reactive gamma-ketoaldehydes, termed isoketals. Analogous compounds have also been shown to be formed from free radical mediated oxidation of docosoahexaenoic acid. Because docosahexaenoic acid is highly enriched in neurons, these compounds have been termed neuroprostanes and neuroketals. An important aspect of the discovery of isoprostanes is that measurement of F2-isoprostanes has emerged as one of the most reliable approaches to assess oxidative stress status in vivo, providing an important tool to explore the role of oxidative stress in the pathogenesis of human disease. Measurement of F4-neuroprostanes has also proved of value in exploring the role of oxidative stress in neurodegenerative diseases. Products of the isoprostane pathway have been found to exert potent biological actions and therefore may participate as physiological mediators of disease.
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            Exhaled 8-isoprostane as an in vivo biomarker of lung oxidative stress in patients with COPD and healthy smokers.

            M. Corradi, V Collins, G Ciabattoni … (2000)
            Most of the studies linking chronic obstructive pulmonary disease (COPD) with oxidative stress are in vitro, using invasive techniques, or measuring systemic oxidative stress. The aim of this study was to quantify oxidative stress in the lungs in patients with COPD and in healthy smokers, as reflected by 8-isoprostane concentrations in breath condensate. This is a noninvasive method to collect airway secretions. 8-Isoprostane is a prostaglandin-F(2alpha) isomer that is formed in vivo by free radical-catalyzed peroxidation of arachidonic acid. We also studied the acute effect of smoking on exhaled 8-isoprostane in healthy smokers. Exhaled 8-isoprostane was measured by a specific enzyme immunoassay in 10 healthy nonsmokers and 12 smokers, 25 COPD ex-smokers, and 15 COPD current smokers. 8-Isoprostane concentrations were similar in COPD ex-smokers (40 +/- 3.1 pg/ml) and current smokers (45 +/- 3.6 pg/ ml) and were increased about 1.8-fold compared with healthy smokers (24 +/- 2.6 pg/ml, p < 0.001), who had 2.2-fold higher 8-isoprostane than healthy nonsmokers (10.8 +/- 0.8 pg/ml, p < 0.05). Smoking caused an acute increase in exhaled 8-isoprostane by about 50%. Our study shows that free radical production is increased in patients with COPD and that smoking causes an acute increase in oxidative stress.
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              The prognostic importance of left ventricular geometry in uremic cardiomyopathy.

              J Harnett, P Parfrey, Brendan D. Murray … (1995)
              The objective of this study was to determine the effect of left ventricular (LV) mass, volume, and mass-to-volume ratio on mortality in chronic dialysis patients. The Design was a multicenter, prospective inception cohort study with a median follow-up of 41 months. The Setting was three university-affiliated nephrology units. A total of 433 patients who (1) survived > 6 months from the start of ESRD therapy and (2) had a technically satisfactory baseline echocardiogram were studied. Measurements included a baseline clinical, laboratory and echocardiographic assessment. LV hypertrophy was present in 74% and LV dilation was present in 36% of patients. In patients with normal cavity volume ( 120 g/m2) and mass-to-volume ratios (> 2.2 g/mL) were independently associated with late mortality (> 2 yr after starting dialysis therapy). After adjusting for baseline age, diabetes, and ischemic heart disease, the relative risk for the former was 3.29 and for the latter was 2.24. Cavity volume was of no prognostic significance in this group. In patients with LV dilation and normal systolic function, high cavity volume (> 120 mL/m2) and low mass-to-volume ratio (< 1.8 mL/m2) were independently associated with late mortality, the relative risk in the former being 17.14 and the latter being 4.27. LV mass index was of no prognostic significance in this group. The baseline echocardiographic classification, based on LV mass and cavity volume, was the strongest predictor of late mortality, after adjusting for age, gender, diabetes mellitus, coronary artery disease, angina pectoris, chronic hypertension, and hemoglobin and serum albumin levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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                Author and article information

                Journal
                Journal ID (nlm-ta): Biomark Insights
                Journal ID (publisher-id): Biomarker Insights
                Title: Biomarker Insights
                Publisher: Libertas Academica
                ISSN (Electronic): 1177-2719
                Publication date Collection: 2008
                Publication date (Electronic): 27 May 2008
                Volume: 3
                Pages: 419-428
                Affiliations
                [1 ] Department of Pathological Biochemistry, Otto-von-Guericke-University of Magdeburg
                [2 ] KortexMed Research Institute of Physiotherapy and Gerontology, Bad Harzburg
                [3 ] Department of Nephrology and Medical Intensive Care, Charité University Clinic of Berlin, Germany and
                [4 ] CNR-IFC, National Council of Research Institute of Clinical Physiology, Pisa, Section of Lecce; A.U.S.L/LE, Lecce, Italy
                Author notes
                Correspondence: Ingrid Wiswedel, Otto-von-Guericke-University, Medical Faculty, Department of Pathological Biochemistry, Leipziger Str. 44, 39120 Magdeburg, Germany. Tel: +49-391-6713638; Fax: +49-391-6713639; Email: ingrid.wiswedel@ 123456med.ovgu.de
                Article
                Publisher ID: bmi-03-419
                PMC ID: 2688378
                PubMed ID: 19578522
                SO-VID: 4d29702c-1f9b-497f-8a93-ff5cc2697e2b
                Copyright © © 2008 by the authors
                License:

                This article is published under the Creative Commons Attribution By licence. For further information go to: http://creativecommons.org/licenses/by/3.0.

                History
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Clinical chemistry
                Keywords: end-stage renal disease (esrd),f2-isoprostanes,c-reactive protein,hemodialysis patients,4-hydroxynonenal,renal anemia
                Data availability:
                ScienceOpen disciplines: Clinical chemistry
                Keywords: end-stage renal disease (esrd), f2-isoprostanes, c-reactive protein, hemodialysis patients, 4-hydroxynonenal, renal anemia

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