Hyponatremia and Hepatorenal Syndrome

Abstract

Hyponatremia and hepatorenal syndrome are severe complications in patients with cirrhosis and ascites resulting from circulatory abnormalities (splanchnic and systemic vasodilatation) that develop with portal hypertension. Both conditions are associated with an increased risk of death. Hyponatremia and renal failure may develop in patients with cirrhosis due to causes other than portal hypertension. Making an accurate differential diagnosis is important both therapeutically and prognostically. In this article, we discuss the pathophysiology, diagnosis, differential diagnosis, and management of hyponatremia and hepatorenal syndrome in patients with cirrhosis.

Keywords: Hyponatremia; ascites; cirrhosis; hepatorenal syndrome.

Figure 1

The pathophysiology of hyponatremia and hepatorenal syndrome (HRS) in cirrhosis. Cirrhosis and portal hypertension lead to the development of splanchnic and systemic vasodilatation that causes a decrease in effective circulatory volume, which in turn leads to the activation of various vasoconstrictor and antinatriuretic neurohumoral systems (renin-angiotensin-aldosterone system, sympathetic nervous system, and nonosmotic release of antidiuretic hormone). This initially leads to water and salt retention increasing intravascular volume and allowing for the continuous formation of ascites. However, with worsening cirrhosis (or with precipitant factors), splanchnic/systemic vasodilatation worsens, leading to a significant increase in antidiuretic hormone release and water retention (in excess of sodium retention) and, thereby, to dilutional hyponatremia. Maximal vasodilatation and activation of vasoconstrictive systems (renin-angiotensin) lead to renal vasoconstriction and the development of HRS. AVP, arginine vasopressin.

Figure 2

Potential therapeutic targets for the management of hyponatremia based on its pathophysiology. AVP, arginine vasopressin; IV, intravenous.

Figure 3

An approach to the hospitalized patient with cirrhosis and acute kidney injury (AKI). AIN, acute interstitial nephritis; ATN, acute tubular necrosis; CKD, chronic kidney disease; FeNa, fractional excretion of sodium; GN, glomerulonephritis; HRS, hepatorenal syndrome; LVP, large-volume paracentesis; MAP, mean arterial pressure; PRA, plasma renin activity.

Figure 4

Management of hepatorenal syndrome based on reversing the main pathophysiologic mechanisms. GFR, glomerular filtration rate; IV, intravenous.