INTRODUCTION

The hepatorenal syndrome is one of many potential causes of acute kidney injury in patients with acute or chronic liver disease. Affected patients usually have portal hypertension due to cirrhosis, severe alcoholic hepatitis, or (less often) metastatic tumors, but can also have fulminant hepatic failure from any cause [1-3]. The hepatorenal syndrome represents the end-stage of a sequence of reductions in renal perfusion induced by increasingly severe hepatic injury. The hepatorenal syndrome is a diagnosis of exclusion and is associated with a poor prognosis.

This topic will review the hepatorenal syndrome in detail. Overviews of the complications of fulminant hepatic failure and cirrhosis are provided elsewhere. (See "Acute liver failure in adults: Management and prognosis" and "Overview of the complications, prognosis, and management of cirrhosis".)

PATHOGENESIS

Arterial vasodilatation in the splanchnic circulation, which is triggered by portal hypertension, appears to play a central role in the hemodynamic changes and the decline in renal function in cirrhosis [1-3]. The presumed mechanism is increased production or activity of vasodilators, mainly in the splanchnic circulation, with nitric oxide thought to be most important [1,4,5].

As the hepatic disease becomes more severe, there is a progressive rise in cardiac output and fall in systemic vascular resistance; the latter change occurs despite local increases in renal and femoral vascular resistance that result in part from hypotension-induced activation of the renin-angiotensin and sympathetic nervous systems (figure 1) [1-3,6]. Thus, the reduction in total vascular resistance results from decreased vascular resistance in the splanchnic circulation [6], perhaps in part under the influence of nitric oxide derived from the endothelium. Bacterial translocation from the intestine into the mesenteric lymph nodes may play an important role in this process [1,7,8]. A review of the hemodynamic changes seen with progressive cirrhosis can be found in a separate topic review. (See "Pathogenesis of ascites in patients with cirrhosis".)

The decline in renal perfusion in this setting is associated with reductions in glomerular filtration rate (GFR) and sodium excretion (often to less than 10 meq/day in advanced cirrhosis) [9,10] and a fall in mean arterial pressure, despite the intense renal vasoconstriction [10]. The importance of splanchnic vasodilatation in these changes can be indirectly illustrated by the response to ornipressin, an analog of antidiuretic hormone (arginine vasopressin) that is a preferential splanchnic vasoconstrictor [11].