Hepatorenal syndrome (HRS) is a syndrome of progressive renal insufficiency without underlying renal parenchymal damage in a cirrhotic patient. In patients with decompensated cirrhosis, the risk of developing HRS is 8%-20% per year. In patients with HRS, renal vasoconstriction occurs in the absence of reduced cardiac output and blood volume with vasoconstriction secondary to the activation of the renin-angiotensin activating system and sympathetic nervous system. Patients with cirrhosis and portal hypertension also exhibit low arterial pressure and reduced systemic vascular resistance.

Risk factors for development of HRS include hyponatremia, low urine sodium, hyperkalemia, large volume paracentesis (> 5 L removal), drug-induced nephrotoxicity, acute liver failure, decompensated cirrhosis (spontaneous bacterial peritonitis, bleeding esophageal varices), or, as a complication, post-transjugular intrahepatic portosystemic shunts (TIPS).

Presentation varies between type 1 and type 2 HRS. In both types, patients present with low urine output and rising serum creatinine values:

• Type 1 HRS – Progressive, acute renal failure (creatinine > 2.5 mg/dL or 50% reduction in glomerular filtration rate [GFR]) over a 2-week period. Often triggered by infection. Poor prognosis with a 10% 90-day survival rate.
• Type 2 HRS – Moderate and stable reduction in GFR that occurs in patients with relatively preserved hepatic function and diuretic resistance. Can precipitate type 1 HRS. More favorable prognosis than type 1 HRS; median survival 6-8 months.

HRS is a diagnosis of exclusion. Diagnostic criteria:

• Acute kidney injury with increase in serum creatinine of 0.3 mg/dL or more within 48 hrs or an increase of greater than 50% from baseline within 7 days.
• Other definitions include a serum creatinine > 1.5 mg/dL or 24-hour creatinine clearance < 40 mL/min.
• Absence of shock, fluid losses, ongoing bacterial infection, or use of nephrotoxic medications.
• No improvement in renal function despite plasma expansion with intravenous (IV) albumin (1 g/kg of body weight up to 100 g/day for 2 days) and/or diuretic withdrawal.
• Proteinuria < 500 mg/day and no ultrasonographic evidence of uropathy or intrinsic parenchymal disease.