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      Limitations of CA125 as an Index of Peritoneal Mesothelial Cell Mass

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          Abstract

          Background: CA125 is commonly used as an index of the mesothelial cell mass in patients treated with peritoneal dialysis. However, we have no data that show a direct relationship between the number of mesothelial cells, their functional properties, and the amount of CA125 produced in these cells. Methods: Experiments were performed on primary in vitro cultures of human peritoneal mesothelial cells obtained from 32 donors of various ages and of both sexes. Spontaneous release of CA125 from the confluent mesothelial cells was measured and correlated with the number of cells in monolayers and with their functional properties. We also studied acute effects of cytokines (IL-1β, TNF-α, and INF-γ) and the chronic effects of glucose (45 m M) on the CA125 content in mesothelial cells and the release of this antigen from their cytosol. Results: Cells from older donors released more CA125, but we found no correlation between the number of cells and the amount of CA125 released from their cytosol. The synthesis of CA125 in mesothelial cells does not correlate with the amount of monocyte chemoattractant protein 1 or interleukin-6 produced in these cells. Acute exposure to cytokines did not modify CA125 content or its release from mesothelial cells. Chronic exposure of mesothelial cells for 4 weeks to glucose (45 m M) decreased the CA125 content of their cytosol and the release of this antigen into the culture medium. Mannitol, at the same concentration and under the same conditions, did not produce these effects, namely a decrease in the CA125 content in the cytosol or its release into the cultural medium. Conclusions: The amount of CA125 released from mesothelial cells is not a good index of their number or their functional properties, because the CA125 release depends not only on the number of cells, but also on their properties. Furthermore, the process is affected by the age of the cell donor and environmental factors such as a high glucose content. The results of this study show the limitations of CA125 as an index of the mesothelial cell mass and viability.

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          Most cited references 14

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          Il-6 and its soluble receptor orchestrate a temporal switch in the pattern of leukocyte recruitment seen during acute inflammation.

          During acute inflammation, leukocyte recruitment is characterized by an initial infiltration of neutrophils, which are later replaced by a more sustained population of mononuclear cells. Based on both clinical and experimental evidence, we present a role for IL-6 and its soluble receptor (sIL-6R) in controlling this pattern of leukocyte recruitment during peritoneal inflammation. Liberation of sIL-6R from the initial neutrophil infiltrate acts as a regulator of CXC and CC chemokine expression, which contributes to a suppression of neutrophil recruitment and the concurrent attraction of mononuclear leukocytes. Soluble IL-6R-mediated signaling is therefore an important intermediary in the resolution of inflammation and supports transition between the early predominantly neutrophilic stage of an infection and the more sustained mononuclear cell influx.
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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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              Bicarbonate/lactate-based peritoneal dialysis solution increases cancer antigen 125 and decreases hyaluronic acid levels.

              In a randomized, controlled trial comparing a pH neutral, bicarbonate/lactate (B/L)-buffered PD solution to conventional acidic, lactate-buffered solution (C), the overnight dialysate levels of markers of inflammation/wound healing [hyaluronic acid (HA)], mesothelial cell mass/membrane integrity [cancer antigen 125 (CA125)], and fibrosis [transforming growth factor-beta1 (TGF-beta1) and procollagen I peptides (PICP)] were assessed over a six-month treatment period. One hundred six patients were randomized (2:1) to either the B/L group or C group. Overnight effluents were collected at entry into the study (time = 0 all patients on control solution) and then at three and six months after randomization. Aliquots were filtered, stored frozen, and assayed for HA, CA125, TGF-beta1, and PICP. Differences between groups were assessed by repeated-measures analysis of variance for unbalanced data using the SAS procedure MIXED. In patients treated with B/L, there was a significant (P = 0.03) increase in CA125 after six months compared with time = 0 (19.76 +/- 11.8 vs. 24.4 +/- 13.8 U/mL; mean +/- SD; N = 51). In the same group of patients, HA levels were significantly decreased at both three and six months in the B/L-treated group (time = 0, 336.0 +/- 195.2; time = 3 months, 250.6 +/- 167.6; and time = 6 months, 290.5 +/- 224.6 ng/mL; mean +/- SD; P = 0.006, N = 47 and P = 0.003, N = 48, respectively). No significant changes in CA125 or HA levels were observed in the control group. There were no significant changes observed in the levels of PICP or TGF-beta1 in the B/L or C group over the six-month treatment period. These results suggest that continuous therapy with the B/L solutions modulates the levels of putative markers of peritoneal membrane integrity and inflammation. In the long term, this may positively impact the peritoneal membrane, increasing its life as a dialyzing organ.
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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
                June 2005
                08 April 2005
                : 100
                : 2
                : c46-c51
                Affiliations
                aDepartment of Pathophysiology, Poznan Medical School, Poznan, Poland;
                Article
                85032 Nephron Clin Pract 2005;100:c46–c51
                10.1159/000085032
                15818058
                © 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: 1, References: 24, Pages: 1
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/85032
                Categories
                Original Paper

                Cardiovascular Medicine, Nephrology

                Glucose, Cytokines, Mesothelial cell mass, CA125

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