Twenty one percent of patients with cirrhosis had a serum sodium level AZD3965 chemical structure of ≤ 130 mmol/L. Patients with hyponatremia had worse ascites that was more difficult to treat, and were more likely to suffer from hepatic encephalopathy and hepatorenal syndrome. Patients with a serum Na ≤130 mmol/L, despite the presence of more ascites, were more likely to be off diuretics compared to those with higher serum Na levels, suggesting diuretics had been stopped in the former because of the hyponatremia.3 The development of hyponatremia is also a marker of an increased risk of death in cirrhosis

independent of the MELD score.4, 5 Lastly, patients with hyponatremia undergoing liver transplantation appear to be at increased risk of neurologic injuries, renal failure and infections in the immediate post-transplant period.6 Hence, hyponatremia is common in cirrhosis, is associated with more severe complications of portal hypertension, complicates

the management of the ascites, and its development indicates a poor prognosis for the patient. Hyponatremia is difficult to treat. The approach used for most patients is fluid restriction. This is a difficult treatment for both the patients and the physician and is of limited effectiveness even in an inpatient environment. For example, in one report serum sodium failed to rise over 7 days of fluid restriction, (1.5 L daily) in patients hospitalized and receiving diuretics.7 Even if GDC-0199 datasheet the serum sodium rises the rate of increase is usually slow and if the hyponatremia is severe, <125 mmol/L, a prolonged hospitalization may be required. Also during this period diuretics are frequently held leading to worsening

ascites. More rapid correction can be achieved with the infusion of hypertonic saline. However, this will worsen the fluid retention and puts the patient at risk for development of hypernatremia and osmotic demyelination. A number of other agents including demeclocycline, urea, and kappa-opioids have been used to correct hyponatremia in cirrhosis but complications of therapy have lead to their abandonment.8 The development of a new class of drugs that block the effects of AVP on the renal tubule medchemexpress has lead to hope that a new and effective therapy is now available for the patient with cirrhosis and hyponatremia. The effect of AVP on water homeostasis is mediated via its effect on water transport by the principle cells in the collecting duct. AVP binds to the V2 receptor on the basolateral membrane of the principle cells leading to activation of the Gs-coupled adenylyl cyclase system and an increase in levels of cyclic adenosine monophosphate (cAMP). Protein kinase A (PKA) is stimulated by cAMP leading to phosphorylation of preformed aquaporin-2 (AQP2) which is then translocated to the apical membrane making the cells more water permeable (Fig 1A).