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      CC-Chemokine RANTES Is Increased in Serum and Urine in the Early Post-Transplantation Period of Human Renal Allograft Recipients

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          Abstract

          Background: The chemokine RANTES is a potent chemoattractant for T cells and monocytes that has been shown to enhance inflammation. The aim of our study was to investigate whether RANTES is upregulated within the early post-transplantation period that may influence short-time allograft function rate. Methods: Serum and urine samples from transplanted renal allograft recipients (n = 17) were obtained from specimens taken for diagnostic reasons. Four patients developed biopsy-proven rejection episodes within the first month. Time course of RANTES was studied within the first 12 days after renal transplantation using ELISA technique. Data were tested for significances between patients with rejection and without rejection, compared to healthy volunteers as controls, and correlated with clinical data. Results: In the control group RANTES concentration was 37.2 ± 2.7 ng/ml (serum) and 8.1 ± 1.3 pg/ml (urine), respectively. In transplanted recipients serum RANTES was significantly upregulated up to 132 ± 28 ng/ml on day 1 after transplantation and remained elevated within the first 12 days (n = 17). Time course of urine RANTES demonstrated elevated concentrations with 754 ± 115 pg/ml on day 1 followed by an continuous decrease to 22.3 ± 7 pg/ml on day 12 (n = 17). No significant differences could be detected between patients with rejection and without rejection episodes. Conclusions: In contrast to data of other urinary marker molecules (like IL-6), there are no significant differences between the rejection and non-rejection group. RANTES is therefore not suitable for early detection of rejection. Nevertheless, serum and urine RANTES concentrations were highly elevated in freshly transplanted renal allograft recipients reflecting an activated immune system.

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          Most cited references 14

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          LRISK FACTORS FOR CHRONIC REJECTION IN RENAL ALLOGRAFT RECIPIENTS

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            Early application of Met-RANTES ameliorates chronic allograft nephropathy.

            Initial insults to kidney allografts, characterized by infiltration of mononuclear inflammatory cells, contribute to chronic allograft nephropathy. Chemokines such as RANTES (regulated upon activation, normal T cell expressed) are thought to be responsible for the recruitment and activation of infiltrating cells. The present study investigated whether early application of Met-RANTES, a chemokine receptor antagonist that blocks the effects of RANTES, can protect renal allografts from long-term deterioration. Fisher (F344) rat kidneys were orthotopically transplanted into Lewis recipients and treated with cyclosporine A (1.5 mg/kg/day) for the first 10 days following transplantation, together with either Met-RANTES at 40 microg/day, 200 microg/day or vehicle for the first 7 days. Animals were harvested at 2 and 28 weeks after transplantation for histologic, immunohistologic and molecular analysis. Met-RANTES treatment reduced the infiltration of lymphocytes and macrophages in allografts at 2 weeks after transplantation, accompanied by decreased mRNA expression of interleukin (IL)-2, IL-1beta, tumor necrosis factor-alpha (TNF-alpha) and RANTES. At post-transplantation week 28, Met-RANTES treatment at high and low doses reduced urinary protein excretion and significantly ameliorated glomerulosclerosis, interstitial fibrosis, tubular atrophy, intimal proliferation of graft arteries and mononuclear cell infiltration. However, creatinine clearance was not influenced by Met-RANTES. Furthermore, Met-RANTES suppressed the mRNA expression of transforming growth factor-beta (TGF-beta) and platelet-derived growth factor-B (PDGF-B). Blockade of chemokine receptors by Met-RANTES diminishes early infiltration and activation of mononuclear cells in the grafts, and thus reduces the pace of chronic allograft nephropathy.
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              RANTES chemokine expression in cell-mediated transplant rejection of the kidney

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                Author and article information

                Journal
                KBR
                Kidney Blood Press Res
                10.1159/issn.1420-4096
                Kidney and Blood Pressure Research
                S. Karger AG
                1420-4096
                1423-0143
                2005
                December 2004
                11 January 2005
                : 28
                : 1
                : 48-54
                Affiliations
                aDepartment of Nephrology, University Frankfurt, Frankfurt/Main, and bDepartment of Nephrology and Rheumatology, University of Göttingen, Göttingen, Germany
                Article
                81774 Kidney Blood Press Res 2005;28:48–54
                10.1159/000081774
                15509902
                © 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: 2, Tables: 3, References: 29, Pages: 7
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/81774
                Categories
                Original Paper

                Cardiovascular Medicine, Nephrology

                RANTES, Renal allograft, Transplantation

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