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      Vasopressin Antagonists: Role in the Management of Hyponatremia

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          Abstract

          Hyponatremia is a common electrolyte disorder associated with potentially serious or life-threatening consequences. Serum osmolality and sodium concentration [Na<sup>+</sup>] are regulated by thirst, the hormone arginine vasopressin (AVP), and renal water and sodium handling. Hyponatremia is frequently caused by dysregulation of AVP, which accompanies disorders of water retention, such as congestive heart failure (CHF) and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Clinical trials with AVP receptor antagonists have confirmed the important role of AVP in the pathophysiology of hyponatremia and suggest these agents are efficacious in treating hyponatremia associated with SIADH, cirrhosis, and CHF. Acting directly at AVP receptors in the renal tubules, these agents promote aquaresis – the electrolyte-sparing excretion of free water – in patients with hyponatremia. In clinical trials, AVP receptor antagonists have been shown to increase the serum [Na<sup>+</sup>] and urine output while decreasing urine osmolality.

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          Most cited references40

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          The syndrome of inappropriate secretion of antidiuretic hormone.

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            Effects of tolvaptan, a vasopressin antagonist, in patients hospitalized with worsening heart failure: a randomized controlled trial.

            Nearly 1 million hospitalizations for chronic heart failure occur yearly in the United States, with most related to worsening systemic congestion. Diuretic use, the mainstay therapy for congestion, is associated with electrolyte abnormalities and worsening renal function. In contrast to diuretics, the vasopressin antagonist tolvaptan may increase net volume loss in heart failure without adversely affecting electrolytes and renal function. To evaluate the short- and intermediate-term effects of tolvaptan in patients hospitalized with heart failure. Randomized, double-blind, placebo-controlled, parallel-group, dose-ranging, phase 2 trial conducted at 45 centers in the United States and Argentina and enrolling 319 patients with left ventricular ejection fraction of less than 40% and hospitalized for heart failure with persistent signs and symptoms of systemic congestion despite standard therapy. After admission, patients were randomized to receive 30, 60, or 90 mg/d of oral tolvaptan or placebo in addition to standard therapy, including diuretics. The study drug was continued for up to 60 days. In-hospital outcome was change in body weight at 24 hours after randomization; outpatient outcome was worsening heart failure (defined as death, hospitalization, or unscheduled visits for heart failure) at 60 days after randomization. Median (interquartile range) body weight at 24 hours after randomization decreased by -1.80 (-3.85 to -0.50), -2.10 (-3.10 to -0.85), -2.05 (-2.80 to -0.60), and -0.60 (-1.60 to 0.00) kg in the groups receiving tolvaptan 30, 60, and 90 mg/d, and placebo, respectively (P< or =.008 for all tolvaptan groups vs placebo). The decrease in body weight with tolvaptan was not associated with changes in heart rate or blood pressure, nor did it result in hypokalemia or worsening renal function. There were no differences in worsening heart failure at 60 days between the tolvaptan and placebo groups (P =.88 for trend). In post hoc analysis, 60-day mortality was lower in tolvaptan-treated patients with renal dysfunction or severe systemic congestion. Tolvaptan administered in addition to standard therapy may hold promise for management of systemic congestion in patients hospitalized for heart failure.
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              Age and gender as risk factors for hyponatremia and hypernatremia.

              This study assesses gender and age as independent risk factors for hypo- and hypernatremia and describes the prevalence of hypo- and hypernatremia in different population groups. Details of all serum Na results with accompanying patient demographics for 2 years were downloaded from the laboratory database into Microsoft Access for multiple logistic regression analysis using SPSS. Female gender and age 145, and >165 mmol/l were for acute hospital care patients: 28.2%, 0.49%, 1.43%, and 0.06%; ambulatory hospital care: 21%, 0.17%, 0.53%, and 0.01%; community care: 7.2%, 0.03%, 0.72%, and 145 and >165 mmol/l, respectively) for age >81 years. Male gender was a mild risk factor for Na<136 mmol/l and was otherwise unimportant. Hyponatremia is a common but generally mild condition while hypernatremia is uncommon. Increasing age is a strong independent risk factor for both hypo- and hypernatremia. Gender is not an important risk factor for disturbances of serum Na concentration.
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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
                2006
                September 2006
                15 September 2006
                : 26
                : 4
                : 348-355
                Affiliations
                Department of Medicine, Queen’s University, Kingston, Canada
                Article
                94539 Am J Nephrol 2006;26:348–355
                10.1159/000094539
                16837788
                72d9f019-6791-4e9b-91e0-1e6a4e53abda
                © 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
                : 26 April 2006
                : 07 June 2006
                Page count
                Figures: 2, Tables: 1, References: 56, Pages: 8
                Categories
                In-Depth Topic Review

                Cardiovascular Medicine,Nephrology
                Syndrome of inappropriate secretion of antidiuretic hormone,Vasopressin,Homeostasis,Salt-water balance,Sodium,Hyponatremia,Antidiuretic hormone

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