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      Short-Term Biological Effects of a New and Less Acidic Fluid for Peritoneal Dialysis

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          Abstract

          Background: Conventional peritoneal dialysates are potentially bioincompatible and seem to be a causative factor for peritoneal sclerosis. Recent studies demonstrated that a new type of dialysate has a positive long-term clinical effect on dialysis patients. Methods: In this study, to elucidate the short-term biological effects of a newly developed dialysate of higher pH on the peritoneal membrane, we assessed macrophage proportions and several markers (inflammatory cytokines, cancer antigen 125 (CA125) and albumin) in spent dialysates before and 2 weeks after the change to the new fluid from a conventional fluid. Results: We found that the use of the new dialysate decreased intraperitoneal levels of inflammatory cytokines, CA125 and albumin associated with the decrease of macrophage populations in dialysis effluents. Conclusion: These observations suggest that a new and less acidic fluid reduces pro-inflammatory potential in the peritoneum, and thus affords better preservation of peritoneal membrane integrity in uremic patients on peritoneal dialysis.

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          Inflammation and coronary artery disease.

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            Long-term clinical effects of a peritoneal dialysis fluid with less glucose degradation products.

            Glucose degradation products (GDPs) are cytotoxic in vitro and potentially toxic in vivo during peritoneal dialysis (PD). We are presenting the results of a two-year randomized clinical trial of a new PD fluid, produced in a two-compartment bag and designed to minimize heat-induced glucose degradation while producing a near neutral pH. The effects of the new fluid over two years of treatment on membrane transport characteristics, ultrafiltration (UF) capacity, and effluent markers of peritoneal membrane integrity were investigated and compared with those obtained during treatment with a standard solution. A two-group parallel design with 80 continuous ambulatory peritoneal dialysis patients was used. The patients were randomly assigned to either the new fluid (N = 40) or to a conventional one (N = 40), and were stratified with respect to age, diabetes, and time on PD. Peritoneal transport characteristics were assessed by the Personal Dialysis Capacity (PDCtrade mark) test at 1, 6, 12, 18, and 24 months after inclusion and by weighing the overnight bag daily. Infusion pain and handling were evaluated using a questionnaire. Peritoneal mesothelial and interstitial integrity were evaluated by analyzing overnight effluent dialysate concentrations of CA 125, hyaluronan (HA), procollagen-1-C-terminal peptide (PICP), and procollagen-3-N-terminal peptide (PIIINP) at 1, 6, 12, 18, and 24 months. The handling of the new two-compartment bag was considered easy, and there were no indications of increased discomfort with the new system. Furthermore, no changes in peritoneal fluid or solute transport characteristics were observed during the study period for either fluid, and neither were there any differences with regard to peritonitis incidence. However, significantly higher dialysate CA 125 (73 +/- 41 vs. 25 +/- 18 U/mL), PICP (387 +/- 163 vs. 244 +/- 81 ng/mL), and PIIINP (50 +/- 24 vs. 29 +/- 13 ng/mL) and significantly lower concentrations of HA (395 +/- 185 vs. 530 +/- 298 ng/mL) were observed in the overnight effluent during treatment with the new fluid. We conclude that the new fluid with a higher pH and less GDPs is safe and easy to use and has no negative effects on either the frequency of peritonitis or peritoneal transport characteristics as compared with conventional ones. Our results indicate that the new solution causes less mesothelial and interstitial damage than conventional ones; that is, it may be considered more biocompatible than a number of conventional PD solutions currently in use.
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              Leukocyte migration across human peritoneal mesothelial cells is dependent on directed chemokine secretion and ICAM-1 expression.

              Leukocyte migration into the peritoneal cavity is a diagnostic feature of peritonitis in patients treated with peritoneal dialysis (PD). While neutrophil (PMN) influx is characteristic of the acute phase of peritoneal infection, significant mononuclear cell (MNC) infiltration, occurs throughout the whole period of infection. Recent data suggests that human peritoneal mesothelial cell (HPMC) adhesion molecule expression and the synthesis of chemotactic cytokines may be important in the process. In the present study we have examined, the regulation and directed secretion of chemokines (IL-8, MCP-1 and RANTES) and the basolateral to apical migration of unstimulated leukocytes across mesothelial cell monolayers using an in vitro model where HPMC were grown on the porous membrane of tissue culture inserts. Separate experiments have defined the importance of chemokine synthesis and ICAM-1 expression in the transmigration process. Apical stimulation of HPMC with IL-1 beta or TNF alpha resulted in a time and dose dependent up-regulation of IL-8, MCP-1 and RANTES mRNA expression and synthesis. This secretion was predominately into the apical compartment (> 85%) with all chemokines. Apical pre-stimulation of HPMC resulted in a dose- and time-dependent migration of both PMN and MNC across HPMC. Neutrophil migration was significantly reduced in the presence of appropriate concentrations of polyclonal IL-8 antibody (IL-1 beta (100 pg/ml) 153 +/- 12 versus anti-IL-8 (100 ng/ml) 71 +/- 7 (X 10(3)) PMN, N = 6, P < 0.02) and in the presence of anti-ICAM-1 F(ab)'2 fragments or soluble ICAM-1. Constitutive and cytokine stimulated mononuclear cell migration was significantly reduced in the simultaneous presence of polyclonal MCP-1 or RANTES antibody. These data demonstrate that HPMC synthesize IL-8, MCP-1 and RANTES in response to inflammatory cytokines. HPMC-derived C-x-C and C-C chemokines might contribute to the intra-peritoneal recruitment of leukocytes during peritoneal inflammation.
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                Author and article information

                Journal
                BPU
                Blood Purif
                10.1159/issn.0253-5068
                Blood Purification
                S. Karger AG
                0253-5068
                1421-9735
                2003
                2003
                29 August 2003
                : 21
                : 4-5
                : 287-293
                Affiliations
                aDepartment of Hemodialysis, Chukyo Hospital, Nagoya, bTerumo Corporation, Tokyo, and cFirst Department of Medicine, Aichi Medical School, Nagakute, Aichi, Japan
                Article
                72547 Blood Purif 2003;21:287–293
                10.1159/000072547
                12944728
                20268d86-b449-4723-8d5a-d7a9756d59ae
                © 2003 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.

                History
                : 20 May 2003
                Page count
                Figures: 5, Tables: 1, References: 42, Pages: 7
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                CA125,Peritoneal dialysis,Dialysate pH,Macrophage,Inflammatory cytokine

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