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      Effects of an Acute Dose of L-Arginine during Coronary Angiography in Patients with Chronic Renal Failure

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          Abstract

          Background: Contrast media (CM) are nephrotoxic and might further worsen renal function in patients with chronic renal failure. L-Arginine, the substrate of nitric oxide, protects kidney function and may improve endothelial function in patients with coronary artery disease. Hypothesis: Acute administration of L-arginine in a subset of patients with combined coronary artery disease and impaired kidney function during coronary angiography might prevent superimposed acute renal failure. Methods: A double-blind study of patients with mild/moderate chronic renal failure (Cr >1.7 mg/dl) undergoing coronary angiography (meglumine ioxaglate) was conducted. Patients received either L-arginine (300 mg/kg) or placebo and were followed for 48 h. Cardiac hemodynamic parameters, renal function and nitric oxide production were sequentially recorded. Results – Primary and Secondary: Both groups experienced a decrease of creatinine clearance 48 h following the procedure (p < 0.05). Creatinine levels slightly increased following the administration of L-arginine (p < 0.05) but not in the placebo treated group. No changes of systemic and cardiac pressures, total peripheral resistance or cardiac output were recorded within and between the treatment and placebo groups. Conclusion: CM injection causes an impairment of renal function. Addition of intravenous L-arginine during cardiac catheterizations in patients with chronic renal failure does not prevent CM-induced nephrotoxicity and does not affect endothelial dysfunction in the particular population studied by the authors, i.e. patients with coronary artery disease (CAD) of various degrees, or suspicion of CAD and chronic mild renal failure.

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          Most cited references 9

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          Effects of saline, mannitol, and furosemide to prevent acute decreases in renal function induced by radiocontrast agents.

          Injections of radiocontrast agents are a frequent cause of acute decreases in renal function, occurring most often in patients with chronic renal insufficiency and diabetes mellitus. We prospectively studied 78 patients with chronic renal insufficiency (mean [+/- SD] serum creatinine concentration, 2.1 +/- 0.6 mg per deciliter [186 +/- 53 mumol per liter]) who underwent cardiac angiography. The patients were randomly assigned to receive 0.45 percent saline alone for 12 hours before and 12 hours after angiography, saline plus mannitol, or saline plus furosemide. The mannitol and furosemide were given just before angiography. Serum creatinine was measured before and for 48 hours after angiography, and urine was collected for 24 hours after angiography. An acute radiocontrast-induced decrease in renal function was defined as an increase in the base-line serum creatinine concentration of at least 0.5 mg per deciliter (44 mumol per liter) within 48 hours after the injection of radiocontrast agents. Twenty of the 78 patients (26 percent) had an increase in the serum creatinine concentration of at least 0.5 mg per deciliter after angiography. Among the 28 patients in the saline group, 3 (11 percent) had such an increase in serum creatinine, as compared with 7 of 25 in the mannitol group (28 percent) and 10 of 25 in the furosemide group (40 percent) (P = 0.05). The mean increase in serum creatinine 48 hours after angiography was significantly greater in the furosemide group (P = 0.01) than in the saline group. In patients with chronic renal insufficiency who are undergoing cardiac angiography, hydration with 0.45 percent saline provides better protection against acute decreases in renal function induced by radiocontrast agents than does hydration with 0.45 percent saline plus mannitol or furosemide.
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            The clinical pharmacology of L-arginine.

            L-Arginine (2-amino-5-guanidinovaleric acid) is the precursor of nitric oxide, an endogenous messenger molecule involved in a variety of endothelium-mediated physiological effects in the vascular system. Acute and chronic administration of L-arginine has been shown to improve endothelial function in animal models of hypercholesterolemia and atherosclerosis. L-Arginine also improves endothelium-dependent vasodilation in humans with hypercholesterolemia and atherosclerosis. The responsiveness to L-arginine depends on the specific cardiovascular disease studied, the vessel segment, and morphology of the artery. The pharmacokinetics of L-arginine have recently been investigated. Side effects are rare and mostly mild and dose dependent. The mechanism of action of L-arginine may involve nitric oxide synthase substrate provision, especially in patients with elevated levels of the endogenous NO synthase inhibitor asymmetric dimethylarginine. Endocrine effects and unspecific reactions may contribute to L-arginine-induced vasodilation after higher doses. Several long-term studies have been performed that show that chronic oral administration of L-arginine or intermittent infusion therapy with L-arginine can improve clinical symptoms of cardiovascular disease in man.
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              Nephrotoxicity related to contrast media.

              The numbers of contrast media (CM)-enhanced examinations are increasing. The annual sale of iodine for CM now represents 60 million CM doses a year world-wide. In spite of improvements in chemical structure, CM are still the third leading cause of hospital-acquired acute renal failure. The definition of contrast nephropathy (CN) is discussed, as well as the mechanisms involved in the pathogenesis. Low osmolar contrast media (LOCM) are less nephrotoxic than high osomolar contrast media (HOCM) and cause fewer osmotoxic side-effects such as pain and heat sensations. The non-ionic dimeric contrast media which are iso-osmolar to plasma (IOCM) cause even fewer haemodynamic side-effects and result in better opacification of the urinary tract than LOCM. The nephrotoxicity of IOCM is low. The risk factors for CN and methods for prevention of CN are discussed.
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                Author and article information

                Journal
                AJN
                Am J Nephrol
                10.1159/issn.0250-8095
                American Journal of Nephrology
                S. Karger AG
                0250-8095
                1421-9670
                2003
                April 2003
                17 January 2003
                : 23
                : 2
                : 91-95
                Affiliations
                aCatheterization Lab, Department of Cardiology, and bDepartment of Nephrology, Tel-Aviv Medical Center, Tel Aviv, Israel
                Article
                68036 Am J Nephrol 2003;23:91–95
                10.1159/000068036
                12481147
                © 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.

                Page count
                Figures: 1, Tables: 3, References: 33, Pages: 5
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/68036
                Categories
                Original Article: Patient-Oriented, Translational Research

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