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      Lymphocyte Apoptosis: Role of Uremia and Permeability of Dialysis Membrane

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          Abstract

          Background: Uremia is associated to host defense mechanism disorders. Lymphocyte apoptosis, which may cause alteration of the immune system, is increased in uremic patients. The aim of the present study was to determine if, in addition to uremia, dialysis membranes with different biocompatibility and permeability have an effect on lymphocyte apoptosis. Methods: Cell apoptosis and Fas expression were assessed using flow cytometry in four groups of patients: (1) uremic non-dialyzed (Non-D) patients; (2) hemodialysis (HD) patients on hemophan; (3) low-flux polysulfone, and (4) high-flux polysulfone membrane. Ten healthy volunteers were used ascontrols. Results: At baseline, lymphocytes from patients on hemophan showed an increase in apoptosis (18.4 ± 6.9%) as compared with Non-D (7.2 ± 2.8%; p < 0.001), low-flux (6.4 ± 2.4%; p < 0.001), high-flux (2.6 ± 1.2%; p < 0.001) and controls (2.0 ± 1.0%; p < 0.001). Fas expression was similar in lymphocytes from Non-D and hemophan dialyzed patients (40.5 ± 5% vs. 40.4 ± 6%), and in both groups it was greater than low-flux (30%±7%; p < 0.001), high-flux (11 ± 4%; p < 0.001) and controls (12.6 ± 3%; p < 0.001). When lymphocytes were cultured for 48 h, apoptosis was similar in Non-D and hemophan (27.0 ± 4.3% vs. 27.1 ± 6.9%); apoptosis of lymphocyte from patients on low-flux (14.1 ± 3.5%) was greater than on high-flux polysulfone membrane (7.0 ± 2.0%; p < 0.001). Conclusion: These findings suggest that in dialysis patients lymphocyte apoptosis is influenced not only by the biocompatibility but also by the permeability of the dialysis membrane.

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          Most cited references 17

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          A novel assay for apoptosis Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V

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            B lymphopenia in uremia is related to an accelerated in vitro apoptosis and dysregulation of Bcl-2.

            Lymphopenia has been described in patients with chronic renal failure (CRF). It is postulated that the decline in lymphocytes is due to accelerated apoptosis. We investigated whether dysregulation of programmed cell death plays a role in the immunodeficiency described in CRF. Peripheral blood lymphocytes (PBL) from pre-dialysis uraemic patients (nHD) and haemodialysed patients (HD) were cultured with no stimulus for 96 h. Apoptosis of lymphocytes was measured by propidium iodide staining and flow cytometry. Expression of Fas and Bcl-2 was also analysed by flow cytometry. Peripheral blood B cells were significantly lower in pre-dialysis and haemodialysis uraemic patients compared to control. Lymphocytes from both groups of patients had a higher rate of apoptosis in vitro than those from healthy controls. This effect was more pronounced in B lymphocytes and a significant correlation between the B lymphopenia and the percentage of apoptotic B cells after 48 h of culture without stimulus was observed. The increased lymphocyte apoptosis in CRF was accompanied by a significantly lower in vitro Bcl-2 expression. However, Fas did not seem to play a role in spontaneous lymphocyte apoptosis in end-stage renal disease. Our data indicate that B lymphopenia in CRF may be partially attributed to an increased susceptibility to cell death by apoptosis that is associated with a decreased expression of Bcl-2.
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              Inflammation and cardiovascular risk in dialysis patients.

              Chronic inflammation, as evidenced by increased levels of C-reactive protein (CRP), predicts all-cause and cardiovascular mortality in hemodialysis patients in short-term studies. Whether CRP is also predictive in the long-term follow-up is unknown.
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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
                July 2005
                15 April 2005
                : 100
                : 3
                : c71-c77
                Affiliations
                aServicio de Nefrología, and bUnidad de Investigación, Hospital Universitario Reina Sofía, Cordoba, Spain
                Article
                85051 Nephron Clin Pract 2005;100:c71–c77
                10.1159/000085051
                15824510
                © 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: 4, Tables: 1, References: 29, Pages: 1
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/85051
                Categories
                Original Paper

                Cardiovascular Medicine, Nephrology

                Lymphocytes, Fas, Hemodialysis membrane, Apoptosis, Uremia

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