Role of vaptans in the management of hydroelectrolytic imbalance in liver cirrhosis

Abstract

Ascites and hyponatremia are the most common complications in patients with liver cirrhosis and develop as a consequence of a severe impairment of liver function and portal hypertension. Increasing evidences support the central role of renal function alterations in the pathogenesis of hydroelectrolytic imbalances in cirrhotic patients, thus implying a dense cross-talk between liver and kidney in the systemic and splanchnic vascular homeostasis in such subjects. Since Arginin Vasopressin (AVP) hyperincretion occurs at late stage of cirrhosis and plays an important role in the development of refractory ascites, dilutional hyponatremia and finally hepato-renal syndrome, selective antagonists of AVP receptors V2 (vaptans) have been recently introduced in the therapeutic algorithm of advanced cirrhotic patients. Despite the promising results of earlier phase-two studies, randomized controlled trials failed to find significant results in terms of efficacy of such drugs both in refractory ascites and hyponatremia. Moreover, concerns on their safety profile arise, due to the number of potentially severe side effects of vaptans in the clinical setting, such as hypernatremia, dehydration, renal impairment, and osmotic demyelination syndrome. More robust data from randomized controlled trials are needed in order to confirm the potential role of vaptans in the management of advanced cirrhotic patients.

Keywords: Arginin vasopressin; Cirrhosis; Liver; Portal hypertension; Vaptans.

Figure 1

Hemodynamic alterations underlying the role of portal hypertension in the ascites, hyponatremia and hepato-renal occurrence in liver cirrhosis. HRS: Hepato-renal syndrome.

Figure 2

Progression of the alterations of renal functionality in cirrhotics. HRS: Hepato-renal syndrome.

Figure 3

Mechanism of action of vaptans. In physiologic conditions, binding of arginine vasopressin to its receptor, raises introcytoplasmatic levels of cyclic adenosine monophosphate, thus resulting in increased expression of aquaporin on the luminal membrane of principal cells in collecting duct. Therefore, free water move down gradient via aquaporin from ductal lumen to blood. Vaptans, by blocking binding of arginine vasopressin to its receptor, inhibit water reabsorption. cAMP: Cyclic adenosine mono-phosphate.