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      Cytokine Production in Haemodialysis

      Blood Purification

      S. Karger AG

      Cytokine, Interleukin, Haemodialysis, Dialytic biocompatibility, Dialysis membrane

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          Abstract

          Many aspects regarding morbidity and mortality of dialysis patients are related to the production of cytokines by peripheral blood mononuclear cells. Clinical alterations resulting from cytokine production and release may include dialysis amyloidosis, malnutrition and atherogenesis. Cytokine release may also play a relevant role in immunodeficiency of dialysis patients by inducing alterations in immune and host-defense system. Interleukin-1, interleukin-6 and tumor necrosis factor are three pro-inflammatory cytokines, mainly produced by monocytes, and involved in pathogenetic aspects of hemodialysis-related diseases. In this review we analyse the mechanisms underlying monocyte activation and describe the different modalities for studying cytokine production and release. Clinical implications of cytokine production are also discussed.

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          Most cited references 4

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          The urea reduction ratio and serum albumin concentration as predictors of mortality in patients undergoing hemodialysis.

          Among patients with end-stage renal disease who are treated with hemodialysis, solute clearance during dialysis and nutritional adequacy are determinants of mortality. We determined the effects of reductions in blood urea nitrogen concentrations during dialysis and changes in serum albumin concentrations, as an indicator of nutritional status, on mortality in a large group of patients treated with hemodialysis. We analyzed retrospectively the demographic characteristics, mortality rate, duration of hemodialysis, serum albumin concentration, and urea reduction ratio (defined as the percent reduction in blood urea nitrogen concentration during a single dialysis treatment) in 13,473 patients treated from October 1, 1990, through March 31, 1991. The risk of death was determined as a function of the urea reduction ratio and serum albumin concentration. As compared with patients with urea reduction ratios of 65 to 69 percent, patients with values below 60 percent had a higher risk of death during follow-up (odds ratio, 1.28 for urea reduction ratios of 55 to 59 percent and 1.39 for ratios below 55 percent). Fifty-five percent of the patients had urea reduction ratios below 60 percent. The duration of dialysis was not predictive of mortality. The serum albumin concentration was a more powerful (21 times greater) predictor of death than the urea reduction ratio, and 60 percent of the patients had serum albumin concentrations predictive of an increased risk of death (values below 4.0 g per deciliter). The odds ratio for death was 1.48 for serum albumin concentrations of 3.5 to 3.9 g per deciliter and 3.13 for concentrations of 3.0 to 3.4 g per deciliter. Diabetic patients had lower serum albumin concentrations and urea reduction ratios than nondiabetic patients. Low urea reduction ratios during dialysis are associated with increased odds ratios for death. These risks are worsened by inadequate nutrition.
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            Blocking IL-1: interleukin 1 receptor antagonist in vivo and in vitro.

            Clinical and experimental evidence suggests that shock, arthritis, osteoporosis, colitis, leukemia, diabetes, wasting and atherosclerosis are mediated, in part, by interleukin 1 (IL-1). Inhibition of this cytokine has been a strategy for studying disease and for new drug development. A naturally-occurring IL-1 inhibitor (IL-1 receptor antagonist, IL-1ra) that blocks binding of IL-1 to its receptors has been cloned and produced in recombinant organisms. IL-1ra reduces the severity of sepsis, colitis, arthritis and diabetes in animals and is presently being tested in humans with arthritis, shock and myelogenous leukemia.
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              Fate of injected interleukin 1 in rats: sequestration and degradation in the kidney.

              The tissue distribution and route of clearance of human recombinant interleukin 1 alpha (IL 1 alpha) injected intravenously in rats was studied. The plasma half-life was approximately 2.5 min, and this was increased after nephrectomy, the kidney being the major organ through which the IL 1 alpha was excreted. Two iodinated fragments of IL 1 alpha, of approximately 5 and 9 kDa, were excreted by the kidneys whereas only intact, 17-kDa IL 1 alpha was detected in plasma, suggesting that the protein was being degraded after uptake by the kidney. The results of in vivo experiments in which surface endopeptidase-24.11 was inhibited with phosphoramidon and in vitro experiments in which rat kidney homogenates were incubated with radiolabeled IL 1 alpha suggest that the cytokine was endocytosed and then hydrolysed by lysosomal proteinases.
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                Author and article information

                Journal
                BPU
                Blood Purif
                10.1159/issn.0253-5068
                Blood Purification
                S. Karger AG
                978-3-8055-6918-7
                978-3-318-00464-9
                0253-5068
                1421-9735
                1999
                1999
                12 August 1999
                : 17
                : 2-3
                : 149-158
                Affiliations
                Department of Nephrology, University Federico II of Naples, Italy
                Article
                14387 Blood Purif 1999;17:149–158
                10.1159/000014387
                10449873
                © 1999 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: 2, References: 146, Pages: 10
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/14387
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