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      Tranilast Slows the Progression of Advanced Diabetic Nephropathy

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          Abstract

          Background: Tranilast, N-(3,4-dimethoxycinnamoyl) anthranilic acid, suppresses collagen synthesis by various cells, including macrophages and fibroblasts, by interfering with the actions of transforming growth factor-beta 1. We investigated the effect of tranilast on progression of diabetic nephropathy (DN), since this process is associated with accumulation of collagens in the glomerulus and interstitium. Methods: Tranilast (100 mg, 3 times daily) was administered to 9 outpatients with advanced DN who were receiving an angiotensin-converting enzyme inhibitor or an angiotensin II receptor antagonist and who exhibited a progressive decline in renal function. The decline in renal function before and during tranilast treatment was evaluated for each patient on the basis of the slope in reciprocal serum creatinine (1/S<sub>Cr</sub>) over time. Urinary type IV collagen (U-IV·C) and protein (U-P) excretions were measured just before commencement of tranilast treatment and every 2 months during the treatment. Results: One male patient dropped out soon after commencement of tranilast treatment due to development of lung cancer, and hemodialysis was introduced in one female patient 6 months after the start of treatment. In the 8 patients who did not drop out, 1/S<sub>Cr</sub> was significantly less steep during tranilast treatment than before treatment (–0.00748 ± 0.00700 vs. –0.01348 ± 0.00636 dl/mg/month, respectively; p = 0.0374). U-IV·C and U-P tended to decrease with time, although the decrease was statistically insignificant. Conclusions: Our data suggest that tranilast treatment may suppress accumulation of collagens in renal tissue and may be therapeutically useful for reducing the progression of advanced DN.

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          Most cited references 4

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          Significance of urinary type IV collagen in patients with diabetic nephropathy using a highly sensitive one-step sandwich enzyme immunoassay

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            Follow-up study on urinary type IV collagen in patients with early stage diabetic nephropathy

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              Inhibitory effect of tranilast on hypertrophic collagen production in the spontaneously hypertensive rat heart.

              Tranilast, N-(3,4-dimethoxycinnamoyl) anthranilic acid, a widely used antiallergy drug in Japan, has been shown to inhibit transforming growth factor-beta1 release from fibroblasts and reduce collagen synthesis in keloid cells. In the present study, we have investigated the effect of this drug on cardiac hypertrophy in spontaneously hypertensive rats (SHR), with a focus on the cardiac collagen matrix, which is associated with myocardial stiffness. Twenty-four-week-old SHRs and Wistar Kyoto rats (WKYs) were administered tranilast (300 mg/kg) orally once a day for 4 weeks. This treatment significantly suppressed increases in left ventricular collagen concentration (P < 0.05) and the left ventricular weight/body weights ratios (P < 0.05) in SHRs, and tranilast was ineffective on collagen concentration and ventricular weight/body weights ratios in WKYs. Tranilast did not affect systolic or diastolic blood pressure, end-diastolic left ventricular pressure and heart rate in both SHRs and WKYs, and the agent did not change positive dp/dt or cardiac output in SHRs. The pressure-volume relationship curve was shifted to the left by the drug; the slope (k) of the logarithm of the pressure-volume relationship curve was significantly increased (P < 0.05) in SHRs. It is concluded that the suppression of increases in cardiac collagen and left ventricular mass by tranilast results in a corresponding prevention of cardiac stiffness as studied in the SHR.
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                Author and article information

                Journal
                NEF
                Nephron
                10.1159/issn.1660-8151
                Nephron
                S. Karger AG
                1660-8151
                2235-3186
                2002
                September 2002
                26 September 2002
                : 92
                : 3
                : 693-698
                Affiliations
                Second Department of Internal Medicine, Iwate Prefectural Central Hospital, Ueda, Morioka, Japan
                Article
                64071 Nephron 2002;92:693–698
                10.1159/000064071
                12372957
                © 2002 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: 3, Tables: 1, References: 40, Pages: 6
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/64071
                Categories
                Preliminary Communication

                Cardiovascular Medicine, Nephrology

                Collagen, Renal failure, Diabetic nephropathy, Tranilast

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