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      Renoprotective Effects of Losartan in Renal Transplant Recipients

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          Abstract

          Background/Aims: Chronic allograft nephropathy is the main cause of late graft loss and nonimmunological factors, including hypertension and proteinuria, the principal etiological factors. In this context, blockage of the renin-angiotensin system could be helpful. The aim of the present study was to review the renoprotective efficacy of losartan in a large group of renal transplant patients undergoing long-term follow-up. Methods: A retrospective analysis of 276 renal transplant patients treated with losartan was performed. The indication for losartan was arterial hypertension in 163 patients, proteinuria in 37 patients and hypertension plus proteinuria in the remaining 76 patients. Clinical and biochemical parameters before starting losartan treatment (–6 months, –3 months and at baseline) and 3, 6, 9, 12, 18 and 24 months after the introduction of losartan were analyzed. Results: Arterial hypertension significantly decreased after the introduction of losartan (p = 0.000). Serum creatinine was significantly decreased by losartan therapy, and changes in the serum creatinine slope (1/sCr) before and after losartan were statistically significant. Proteinuria markedly decreased after the introduction of losartan. Clinical and biochemical tolerance of losartan was excellent in most patients and only 9 out of the 276 patients (3%) treated with losartan discontinued the drug because of an adverse event. During follow-up, only 3 patients required substitutive treatment with dialysis due to progressive deterioration of renal function in the context of chronic allograft nephropathy. Conclusion: Losartan demonstrated high efficacy as a renoprotective agent in renal transplant patients and could be useful in the treatment and prevention of chronic allograft nephropathy.

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          Association of chronic kidney graft failure with recipient blood pressure. Collaborative Transplant Study.

          Immunological rejection is the most important cause of kidney transplant failure. Recently, nonimmunological causes of long-term allograft failure have become more widely appreciated. In primary chronic renal disease, blood pressure is of overriding importance for long-term renal function. The role of blood pressure in determining long-term transplant outcome has not yet been established. We studied the influence of blood pressure post-transplantation on long-term kidney graft outcome in 29,751 patients. Outpatient blood pressure measurements were recorded and reported to the Collaborative Transplant Study. Graft and patient survival rates were analyzed over seven years in relation to blood pressure. Increased levels of systolic and diastolic blood pressure post-transplantation were associated with a graded increase of subsequent graft failure (P < 0.0001). Chronic graft failure was significantly associated with blood pressure even when patient death was censored (P < 0.0001). Cox regression analysis established increased blood pressure as an independent risk factor for graft failure. We conclude that post-transplant blood pressure is a highly significant predictor of long-term kidney graft outcome. Whether aggressive lowering of blood pressure improves long-term transplant outcome will have to be studied prospectively.
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            1999 World Health Organization-International Society of Hypertension Guidelines for the Management of Hypertension

            (1999)
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              Losartan decreases plasma levels of TGF-beta1 in transplant patients with chronic allograft nephropathy.

              Chronic allograft nephropathy represents the principal cause of graft loss after the first year of transplantation. Transforming growth factor-beta1 (TGF-beta1) is a key factor in fibrogenesis and has been involved in the pathogenesis of chronic allograft nephropathy and other chronic nephropathies. Experimental studies have demonstrated that the angiotensin II receptor antagonist (losartan) could decrease the synthesis of TGF-beta1. The aim of this study was to determine the plasma levels of TGF-beta1 in transplant patients with chronic allograft nephropathy, and to evaluate the effect of losartan on TGF-beta1 plasma levels and other vasoactive peptides (angiotensin II, plasma renin activity, aldosterone, endothelin-1, and nitrites and nitrates). Angiotensin-converting enzyme genotypes were also determined in all patients. Fourteen transplant patients with chronic allograft nephropathy were included. Treatment with losartan (50 mg) was introduced. Consecutive determinations of TGF-beta1 and other vasoactive peptides were performed during follow-up. Patients with chronic allograft nephropathy presented higher plasma levels of TGF-beta1 than the control groups. The treatment with losartan significantly decreased the plasma levels of TGF-beta1 (P < 0.05) and endothelin (P < 0.05) in all patients. The decrease of TGF-beta1 was statistically correlated with the blockade of the angiotensin II receptor (P < 0.05). No significant correlation could be demonstrated between angiotensin-converting enzyme genotypes and TGF-beta, endothelin-1, and nitrite-nitrate serum levels. This study demonstrates that losartan significantly decreases the plasma levels of TGF-beta1, the most important fibrogenetic factor. These results could play a decisive role in the treatment and prevention of chronic nephropathies, not only graft nephropathy, because the intrinsic pathogenetic mechanism is very similar in all forms, with a crucial roles for the renal renin-angiotensin system and TGF-beta1.
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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
                2003
                November 2003
                17 November 2004
                : 95
                : 3
                : c84-c90
                Affiliations
                aRenal Transplant Unit, IDIBAPS, Hospital Clinic, Barcelona, bNephrology Department, Hospital de Galdakao, Bilbao, cNephrology Department, Hospital Reina Sofía, Córdoba, and dNephrology Department, Hospital Gregorio Marañón, Madrid, Spain
                Article
                74321 Nephron Clin Pract 2003;95:c84–c90
                10.1159/000074321
                14646368
                a7eac7ad-091a-4a4a-83d6-e3f5ce84d67f
                © 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
                : 26 July 2002
                : 18 August 2003
                Page count
                Tables: 4, References: 26, Pages: 1
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Proteinuria,Chronic allograft nephropathy,Angiotensin II receptor blockers,Hypertension

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