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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 21, 2015; 21(11): 3197-3205
Published online Mar 21, 2015. doi: 10.3748/wjg.v21.i11.3197
Hyponatremia in cirrhosis: Pathophysiology and management
Savio John, Paul J Thuluvath
Savio John, Division of Gastroenterology, Department of Medicine, SUNY Upstate Medical University, Syracuse, NY 13210, United States
Paul J Thuluvath, University of Maryland School of Medicine and Mercy Medical Center, Baltimore, MD 21202, United States
Author contributions: John S reviewed the literature, drafted the manuscript and approved the final version of the article to be published; Thuluvath JP reviewed the literature, made critical revisions related to the content of the article and approved the final version of the article to be published.
Conflict-of-interest: None conflicting interest related to the manuscript submitted for publication.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Paul J Thuluvath, MD, FAASLD, FRCP, Professor of Medicine and Surgery, University of Maryland School of Medicine and Mercy Medical Center, 301 Saint Paul Place, Baltimore, MD 21202, United States. thuluvath@gmail.com
Telephone: +1-410-3329356 Fax: +1-410-7835884
Received: October 20, 2014
Peer-review started: October 21, 2014
First decision: November 14, 2014
Revised: December 2, 2014
Accepted: January 30, 2015
Article in press: January 30, 2015
Published online: March 21, 2015
Abstract

Hyponatremia is frequently seen in patients with ascites secondary to advanced cirrhosis and portal hypertension. The development of ascites in patients with cirrhosis is multi-factorial. Portal hypertension and the associated systemic vasodilation lead to activation of the sodium-retaining neurohumoral mechanisms which include the renin-angiotensin-aldosterone system, sympathetic nervous system and antidiuretic hormone (ADH). The net effect is the avid retention of sodium and water to compensate for the low effective circulatory volume resulting in the development of ascites. Although not apparent in the early stages of cirrhosis, the progression of cirrhosis and ascites leads to impairment of the kidneys to eliminate solute- free water. This leads to additional compensatory mechanisms including non-osmotic secretion of ADH, also known as arginine vasopressin, further worsening excess water retention and thereby hyponatremia. Hyponatremia is associated with increased morbidity and mortality in patients with cirrhosis, and is an important prognostic marker both before and after liver transplant. The management of hyponatremia in this setting is a challenge as conventional therapy for hyponatremia including fluid restriction and loop diuretics are frequently inefficacious. In this review, we discuss the pathophysiology and various treatment modalities, including selective vasopressin receptor antagonists, for the management of hyponatremia in patients with cirrhosis.

Keywords: Hyponatremia in cirrhosis, Dilutional hyponatremia, Hypervolemic hyponatremia, Vasopressin receptor antagonists, Vaptans

Core tip: Hyponatremia is the most common electrolyte abnormality observed in hospitalized patients and is a common finding in patients with advanced cirrhosis. The management of hyponatremia in cirrhosis is challenging as conventional therapy for hyponatremia including fluid restriction and loop diuretics are frequently inefficacious. Vaptans, drugs that selectively antagonizes the effects of arginine vasopressin on the V2 receptors in the kidney tubules, represent a logical step in the treatment of hyponatremia. The currently available vaptans, however, are not approved for use in patients with cirrhosis due to the increased risk for hepatic failure and mortality.