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      Effects of Pravastatin Treatment on Blood Pressure Regulation after Renal Transplantation

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          Abstract

          Background/Aim: Hypertension is one of the main cardiovascular risk factors and has an impact also on long-term kidney graft survival. In addition to their lipid-lowering properties, it was shown that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors also have a blood pressure lowering effect. We examined whether treatment with a statin interferes with blood pressure regulation and antihypertensive treatment after renal transplantation. Methods: 74 patients were treated with initially 20 mg of pravastatin daily immediately after kidney transplantation. This group was compared to a matched cohort of 76 patients without statin treatment. All patients received standard immunosuppressive triple therapy with ciclosporin A microemulsion together with an antiproliferative agent and prednisolone. Primary objective of this analysis was systolic and diastolic blood pressure regulation with and without pravastatin. Furthermore, graft function expressed as creatinine clearance and proteinuria, immunosuppressive regimen, and incidence of cardiovascular events and graft loss were recorded for 48 months. Results: The blood pressure regulation was comparable in both groups; however, to achieve this, significantly more antihypertensive drugs had to be used in the statin-treated patients as compared with the controls (2.9 vs. 2.2 agents at 48 months). A slightly higher ciclosporin A exposure of the statin-treated patients could have contributed to this observation. The graft function after 4 years was comparable between the groups (creatinine clearance 56.9 vs. 57.0 ml/min), and a trend of reduced proteinuria could be demonstrated after 4 years of statin treatment (0.4 vs. 0.9 g/day). The low-density lipoprotein cholesterol levels decreased as expected during treatment (3.1 vs. 3.7 mmol/l at 48 months), but the recommended target levels for patients with a high cardiovascular risk have not been reached. A trend towards lower incidences of acute rejection, chronic allograft nephropathy, and graft loss was noted in the statin-treated group. Adverse effects of statin treatment have not been observed. Conclusion: Treatment with pravastatin at low to average dosages does not result in improved blood pressure regulation after kidney transplantation.

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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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            Post-transcriptional Regulation of Endothelial Nitric Oxide Synthase mRNA Stability by Rho GTPase

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              Effect of Statins on Risk of Coronary Disease

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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
                2006
                January 2007
                16 January 2007
                : 29
                : 6
                : 329-337
                Affiliations
                Division of Nephrology, Department of Internal Medicine I, University Hospital Würzburg, Würzburg, Germany
                Article
                97355 Kidney Blood Press Res 2006;29:329–337
                10.1159/000097355
                17124431
                65a782f4-dd72-4494-9efc-45c5cee3c2ed
                © 2006 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
                Page count
                Figures: 1, Tables: 6, References: 30, Pages: 9
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Kidney transplantation,Blood pressure regulation,Statins,Pravastatin,Pleiotropic effects, statins

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