0
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found

      Cyclosporin A Induces Peritoneal Fibrosis and Angiogenesis during Chronic Peritoneal Exposure to a Glucose-Based, Lactate-Buffered Dialysis Solution in the Rat

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background/Aims: Cyclosporin A (CsA) stimulates the development of fibrosis. We investigated whether CsA contributes to peritoneal alterations induced by long-term exposure to dialysis solutions. Methods: Ten rats received peritoneal infusion of dialysis solution and oral CsA for 8 weeks. Eight received only the dialysis solution (controls). Peritoneal function was assessed at 8 weeks followed by sacrifice. The number of vessels was counted, fibrosis was assessed and hydroxyproline was determined. PCR was performed for vascular endothelial growth factor (VEGF), connective tissue growth factor (CTGF) and transforming growth factor-β (TGF-β). Results: Histology revealed more fibrosis, hydroxyproline and vessels (thick walled) in CsA-exposed animals. Peritoneal transport was not different. The mRNA content of TGF-β, CTGF and VEGF was higher in CsA. Conclusion: CsA combined with exposure to dialysis solutions was associated with increased peritoneal fibrosis and angiogenesis.

          Related collections

          Most cited references 14

          • Record: found
          • Abstract: found
          • Article: not found

          Expression of connective tissue growth factor in human renal fibrosis.

          Chronic renal failure may occur in etiologically diverse renal diseases and can be caused by hemodynamic, immunologic and metabolic factors. Initial damage may evoke irreversible scarring, which involves production of a number of proinflammatory and fibrogenic cytokines, including platelet-derived growth factor (PDGF) and transforming growth factor beta (TGF-beta). Connective tissue growth factor (CTGF), a cytokine of the family of growth regulators comprising sef10, cyr61, CTGF and nov, has recently been described in association with scleroderma and other scarring conditions. We investigated CTGF mRNA expression in 65 human renal biopsy specimens of various renal diseases by in situ hybridization. In control human kidney CTFG mRNA was mainly expressed in visceral epithelial cells, parietal epithelial cells, and some interstitial cells. Connective tissue growth factor was strongly up-regulated in the extracapillary and severe mesangial proliferative lesions of crescentic glomerulonephritis, IgA nephropathy, focal and segmental glomerulosclerosis and diabetic nephropathy. An increase in the number of cells expressing CTGF mRNA was observed at sites of chronic tubulointerstitial damage, which correlated with the degree of damage. in the tubulointerstitial area the majority of the CTGF mRNA positive cells coexpressed alpha-smooth muscle actin, and were negative for macrophage markers. Our results indicate that CTGF may be a common growth factor involved in renal fibrosis.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Cyclosporine-associated chronic nephropathy.

            We evaluated glomerular filtration in 17 recipients of heart transplants who were treated for 12 months or longer with cyclosporine (cyclosporin A). The control group consisted of 15 heart-transplant recipients who were treated with azathioprine and who had also survived for at least 12 months. Despite an equivalent cardiac output, the glomerular filtration rate was depressed (51 +/- 4 vs. 93 +/- 3 ml per minute, P less than 0.005) in transplant recipients treated with cyclosporine. Cyclosporine treatment was also associated with reduced renal plasma flow (320 +/- 21 vs. 480 +/- 30 ml per minute, P less than 0.001). A trend toward restricted transglomerular transport of neutral dextrans (radii, 2.4 to 5.8 nm) in cyclosporine-treated recipients suggested an intrinsic loss of ultrafiltration capacity by glomerular capillaries rather than a hemodynamic basis for the reduced glomerular filtration rate. Histopathologic examination of the kidneys of five cyclosporine-treated patients with glomerular hypofiltration revealed a variable degree of tubulointerstitial injury accompanied by focal glomerular sclerosis. Among the 32 heart-transplant recipients treated for more than 12 months with cyclosporine at our center, end-stage renal failure developed in 2. We conclude that long-term cyclosporine therapy may lead to irreversible and potentially progressive nephropathy. We recommend that cyclosporine be used with restraint and caution until ways are found to mitigate its nephrotoxicity.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Morphologic changes of peritoneum and expression of VEGF in encapsulated peritoneal sclerosis rat models.

              Simple sclerosis consisted of a thin layer of submesothelial sclerotic tissue in peritoneal dialysis patients. Encapsulated peritoneal sclerosis (EPS) was characterized by thick sclerotic tissue involving vascular alterations in peritoneal dialysis patients. The objective of the present study is to evaluate serial morphologic changes and expressions of angiogenic factors [i.e., vascular endothelial growth factor (VEGF), angiopietin-1 (Ang-1), and angiopoietin-2 (Ang-2)] in EPS rat models. Twenty-four rats were given a daily intraperitoneal injection of chlorhexidine gluconate and ethanol dissolved in saline (CH). Nine rats were injected with CH and anti-VEGF neutralizing antibody simultaneously. Quantitative blood vessel evaluation was performed by staining for GS1-lectin. The mRNA expression of VEGF, Ang-1, Ang-2, and their receptors was evaluated by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemical staining was performed in peritoneal vessels using anti-VEGF, Ang-1, and Ang-2 antibodies. Hematopoietic stem cells were detected using anti-CD34 antibody. The vessel area, diameter, and length gradually increased until day 21, and then decreased. VEGF and Ang-2 mRNA expressions gradually increased until day 35. In contrast, Ang-1 peaked at day 21 and then decreased significantly. VEGF blockade improved the experimental EPS. In immunohistochemistry, the vessels stained by VEGF and Ang-2 were detected in subfibrous layer. CD34-positive cells were markedly stained at day 21. Neoangiogenesis was observed in a rat model of experimental EPS. VEGF and angiopoietin/Tie system play an important role in the neoangiogenesis in this model. An analysis using this experimental rat model may elucidate the development of EPS in peritoneal dialysis patients.
                Bookmark

                Author and article information

                Journal
                BPU
                Blood Purif
                10.1159/issn.0253-5068
                Blood Purification
                S. Karger AG
                0253-5068
                1421-9735
                2007
                January 2008
                14 December 2007
                : 25
                : 5-6
                : 466-472
                Affiliations
                Departments of aNephrology, bPathology and cExperimental Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
                Article
                112475 Blood Purif 2007;25:466–472
                10.1159/000112475
                18087149
                © 2007 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, Tables: 6, References: 30, Pages: 7
                Categories
                Orginal Paper

                Cardiovascular Medicine, Nephrology

                Angiogenesis, Peritoneal dialysis, Cyclosporin, Fibrosis

                Comments

                Comment on this article