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      Renal Protective Effects of the Renin-Angiotensin-Aldosterone System Blockade: From Evidence-Based Approach to Perspectives

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          Abstract

          The renin-angiotensin-aldosterone system (RAAS) blockade is currently the best-documented treatment strategy to delay the progression of chronic nephropathies. Angiotensin-converting enzyme inhibitors (CEIs) or angiotensin II type 1 receptor antagonists (ARBs) should be used in every normotensive and hypertensive patient with chronic proteinuric nephropathy of both diabetic and non-diabetic origin. The therapy should be initiated as early as possible, bearing in mind that the renoprotection is more effective if used before overt proteinuria or a reduction in kidney function is present. The therapy should be offered to all patients, regardless of renal function, as well as to subjects with severely impaired glomerular filtration. CEIs and ARBs should be administered in therapeutic doses as high as possible to achieve maximal possible proteinuria reduction and systemic blood pressure target <130/80 mm Hg, and 125/75 mm Hg in those subjects with renal insufficiency who present with proteinuria above 1 g/24 h. The combined therapy with the concomitant use of CEIs and ARBs should be offered to all patients with proteinuric non-diabetic chronic nephropathies who do not achieve full and persistent remission of proteinuria with CEI or ARB alone. The article reviews an evidence-based approach on the use of RAAS-inhibiting agents in kidney diseases, considers treatment strategies in different clinical situations and discusses some perspectives related to the implementation of the RAAS blockade in renal protection.

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          Most cited references 67

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          The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes.

           Ryan Andersen,  P Arner,   (2001)
          Microalbuminuria and hypertension are risk factors for diabetic nephropathy. Blockade of the renin-angiotensin system slows the progression to diabetic nephropathy in patients with type 1 diabetes, but similar data are lacking for hypertensive patients with type 2 diabetes. We evaluated the renoprotective effect of the angiotensin-II-receptor antagonist irbesartan in hypertensive patients with type 2 diabetes and microalbuminuria. A total of 590 hypertensive patients with type 2 diabetes and microalbuminuria were enrolled in this multinational, randomized, double-blind, placebo-controlled study of irbesartan, at a dose of either 150 mg daily or 300 mg daily, and were followed for two years. The primary outcome was the time to the onset of diabetic nephropathy, defined by persistent albuminuria in overnight specimens, with a urinary albumin excretion rate that was greater than 200 microg per minute and at least 30 percent higher than the base-line level. The base-line characteristics in the three groups were similar. Ten of the 194 patients in the 300-mg group (5.2 percent) and 19 of the 195 patients in the 150-mg group (9.7 percent) reached the primary end point, as compared with 30 of the 201 patients in the placebo group (14.9 percent) (hazard ratios, 0.30 [95 percent confidence interval, 0.14 to 0.61; P< 0.001] and 0.61 [95 percent confidence interval, 0.34 to 1.08; P=0.081 for the two irbesartan groups, respectively). The average blood pressure during the course of the study was 144/83 mm Hg in the placebo group, 143/83 mm Hg in the 150-mg group, and 141/83 mm Hg in the 300-mg group (P=0.004 for the comparison of systolic blood pressure between the placebo group and the combined irbesartan groups). Serious adverse events were less frequent among the patients treated with irbesartan (P=0.02). Irbesartan is renoprotective independently of its blood-pressure-lowering effect in patients with type 2 diabetes and microalbuminuria.
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            Effect of Blood Pressure Lowering and Antihypertensive Drug Class on Progression of Hypertensive Kidney DiseaseResults From the AASK Trial

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              Angiotensin-receptor blockade versus converting-enzyme inhibition in type 2 diabetes and nephropathy.

              Few studies have directly compared the renoprotective effects of angiotensin II-receptor blockers and angiotensin-converting-enzyme (ACE) inhibitors in persons with type 2 diabetes. In this prospective, multicenter, double-blind, five-year study, we randomly assigned 250 subjects with type 2 diabetes and early nephropathy to receive either the angiotensin II-receptor blocker telmisartan (80 mg daily, in 120 subjects) or the ACE inhibitor enalapril (20 mg daily, in 130 subjects). The primary end point was the change in the glomerular filtration rate (determined by measuring the plasma clearance of iohexol) between the baseline value and the last available value during the five-year treatment period. Secondary end points included the annual changes in the glomerular filtration rate, serum creatinine level, urinary albumin excretion, and blood pressure; the rates of end-stage renal disease and cardiovascular events; and the rate of death from all causes. After five years, the change in the glomerular filtration rate was -17.5 ml per minute per 1.73 m2 (where the minus sign denotes a decrement) in the telmisartan-treated subjects, as compared with -15.0 ml per minute per 1.73 m2 in the enalapril-treated subjects; the treatment difference was thus -2.6 ml per minute per 1.73 m2 (95 percent confidence interval, -7.1 to 2.0 ml per minute per 1.73 m2)[corrected] The lower boundary of the confidence interval, in favor of enalapril, was greater than the predefined margin of -10.0 ml per minute per 1.73 m2, indicating that telmisartan was not inferior to enalapril. The effects of the two agents on the secondary end points were not significantly different after five years. Telmisartan is not inferior to enalapril in providing long-term renoprotection in persons with type 2 diabetes. These findings do not necessarily apply to persons with more advanced nephropathy, but they support the clinical equivalence of angiotensin II-receptor blockers and ACE inhibitors in persons with conditions that place them at high risk for cardiovascular events. Copyright 2004 Massachusetts Medical Society.
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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 2005
                27 December 2005
                : 28
                : 4
                : 230-242
                Affiliations
                Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdan´sk, Poland
                Article
                87842 Kidney Blood Press Res 2005;28:230–242
                10.1159/000087842
                16127280
                © 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: 3, References: 110, Pages: 13
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/87842
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