Description

• Hepatorenal syndrome (HRS) is a kidney impairment in decompensated liver disease characterized by decreased renal perfusion caused by severe splanchnic vasodilatation in the absence of shock, renal disease, or nephrotoxic effects of medications or other substances.
• HRS has a poor prognosis. Median survival is weeks (rapidly progressive disease, type I) to months (slowly progressive disease, type II) if untreated.
• Liver transplant is the preferred treatment for type I HRS.
• Vasoconstrictors and albumin have been used for type I and type II with variable results. Vaptans (for dilutional hyponatremia), transjugular intrahepatic portosystemic shunt (TIPS) procedure, and hemodialysis can be considered in specific patients.

Epidemiology

Incidence

• 4% in patients admitted with decompensated cirrhosis
• 30% in patients with cirrhosis and concurrent spontaneous bacterial peritonitis (SBP)
• 46% in patients with cirrhosis and renal failure

Etiology and Pathophysiology

• Poorly understood
• Portal hypertension leads to endothelial wall shear stress resulting in nitric oxide production. This causes splanchnic vasodilatation, which reduces effective circulating blood volume.
• Reduction in circulating blood volume leads to activation of renin-angiotensin-aldosterone system and release of vasopressin.
• This leads to renal vasoconstriction as well as retention of Na⁺ and water, ultimately contributing to the development of ascites.
• Compensatory mechanisms cannot overcome marked reduction in volume, and resultant renal vasoconstriction further diminishes renal blood flow.
• Inflammatory response involving mesenteric lymph nodes triggered by bacterial translocation is suspected as factor for vasodilatation.

Genetics
No genetic link has been found.

Risk Factors

• Infections
  • ~30% of patients with SBP develop HRS.
  • Systemic infection
• Cirrhosis
• Gastrointestinal (GI) bleeding
• Large-volume paracentesis without albumin administration may lead to activation of the renin-angiotensin-aldosterone system.

General Prevention

• Early diagnosis and aggressive treatment of infections in cirrhotic patients
• In SBP, administration of albumin (1.5 g/kg at diagnosis and 1 g/kg on day 3) decreases frequency of HRS and improves survival (1)[A],(2).
• Short-term usage (<4 weeks) of pentoxifylline in patients with severe alcoholic hepatitis may prevent HRS (3)[B],(4). Pentoxifylline does not decrease short-term mortality but does reduce complications in patients with advanced cirrhosis.
• Long-term oral norfloxacin (400 mg/day) delays SBP and improves survival in cirrhotics.