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      Intraperitoneal Heparin Ameliorates the Systemic Inflammatory Response in PD Patients

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          Abstract

          Background: Patients with end-stage renal disease (ESRD) suffer from high mortality rates of cardiovascular diseases, conditions closely linked to the magnitude of their chronic low-grade inflammation. As heparins have been suggested to possess anti-inflammatory properties, we set out to investigate the impact of long-term treatment with intraperitoneal heparin on local and systemic inflammation in peritoneal dialysis (PD) patients. Methods: In a double-blinded cross-over study, 21 PD patients with ESRD were randomised to inject either 4,500 anti-Xa IU tinzaparin or placebo (isotonic saline) into their morning dialysis bags every day for two periods of 3 months separated by a 1-month wash-out period. Blood and dialysate samples were analysed for inflammatory markers at the start and end of each treatment period. In dialysate, the appearance rates of the inflammatory markers were calculated to adjust for ultrafiltration variations. Results: Eleven patients completed the trial. Treatment with intraperitoneal tinzaparin was accompanied with a median 25.8% reduction of the plasma C-reactive protein concentration (p = 0.032), a 7.3% reduction of the plasma fibrinogen concentration (p = 0.042) and a 54.5% reduction of the dialysate interleukin 6 appearance rate (p = 0.007) compared with placebo. Conclusion: Long-term treatment with intraperitoneal tinzaparin of ESRD patients on PD reduces local and systemic concentrations of inflammatory markers.

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          Most cited references 11

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          Cardiovascular disease and chronic renal disease: a new paradigm.

          Cardiovascular disease (CVD) is a major cause of morbidity and mortality among patients with chronic renal disease (CRD). Despite Improvement in treatment for CVD over the past 30 years, CVD mortality is approximately 15 times higher in dialysis patients than in the general population. The high prevalence of CVD among Incident dialysis patients suggests that CVD begins in earlier stages of CRD, and that implementation of risk factor reduction strategies earlier in the course of CRD may provide an opportunity to prevent CVD in CRD. Based on parallels between CVD and renal disease progression, we have proposed a paradigm that CVD and CRD are outcomes of the same underlying disorders. We propose that risk factor reduction strategies used to prevent CVD in the general population also be applied to patients with CRD, with the hope of preventing progression of renal disease, as well as preventing CVD.
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            C-reactive protein, interleukin-6, and fibrinogen as predictors of coronary heart disease: the PRIME Study.

            This study was undertaken to examine the association of plasma inflammatory markers such as C-reactive protein (CRP), interleukin-6, and fibrinogen with the incidence of coronary heart disease within the prospective cohort study on myocardial infarction (PRIME study). Multiple risk factors were recorded at baseline in 9758 men aged 50 to 59 years who were free of coronary heart disease (CHD) on entry. Nested case-control comparisons were carried out on 317 participants who suffered myocardial infarction (MI)-coronary death (n=163) or angina (n=158) as an initial CHD event during a follow-up for 5 years. After adjustment for traditional risk factors, incident MI-coronary death, but not angina, was significantly associated with CRP, interleukin-6, and fibrinogen, but only interleukin-6 remained significantly associated with MI-coronary death when the 3 inflammatory markers were included in the model. The different interleukin-6 levels in Northern Ireland and France partly explained the difference in risk between these countries. Interleukin-6 appeared as a risk marker of MI-coronary death, and it improved the definition of CHD risk beyond LDL cholesterol. This association may reflect the underlying inflammatory reaction located in the atherosclerotic plaque or a genetic susceptibility on the part of CHD subjects to answer a proinflammatory stimulus and subsequent increase in hepatic CRP gene expression.
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              Cardiovascular risk in uraemic patients-is it fully explained by classical risk factors?

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                Author and article information

                Journal
                NEC
                Nephron Clin Pract
                10.1159/issn.1660-2110
                Nephron Clinical Practice
                S. Karger AG
                1660-2110
                2005
                August 2005
                22 April 2005
                : 100
                : 4
                : c105-c110
                Affiliations
                Departments of aClinical Biochemistry and bNephrology, Ribe County Hospital, and cDepartment for Thrombosis Research, University of Southern Denmark, Esbjerg, Denmark
                Article
                85289 Nephron Clin Pract 2005;100:c105–c110
                10.1159/000085289
                15849476
                © 2005 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 3, Tables: 2, References: 20, Pages: 1
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/85289
                Categories
                Original Paper

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