Hepatorenal Syndrome

Overview

Etiology

Hepatorenal syndrome is associated with portal hypertension due to:

• Cirrhosis
• Severe alcoholic hepatitis
• Metastatic tumors
• Any cause of fulminant liver failure

Classification

There are 2 types of hepatorenal syndrome:

1. Type 1: progressive impairment in renal function and a significant reduction in creatinine clearance within 1–2 weeks
2. Type 2 
   • Renal impairment that is less severe than seen in type 1 HRS
   • Associated with a better outcome and ascites that is resistant to diuretics

Pathophysiology

1. Portal hypertension triggers arterial vasodilation in the splanchnic circulation.
2. This causes: ascites → arterial hypovolemia → activation of renin-angiotensin-aldosterone system (RAAS)
3. Activation of RAAS causes: renal vasoconstriction → hypoperfusion of the kidneys → oliguria → anuria → progressive kidney failure 

Trigger factors are any interventions or conditions that cause arterial hypovolemia:

• Drainage of ascites
• Bacterial infection 
• Gastrointestinal bleeding
• Excessive use of diuretics

Clinical Presentation and Diagnosis

Clinical presentation

• New-onset signs of renal failure with no other identifiable cause:
  • Oliguria → anuria → acute kidney failure 
  • In the early phase of HRS, urine output is often normal.
• Signs of water retention:
  • Edema
  • Ascites
  • Pleural effusion
• Signs and symptoms of cirrhosis:
  • Jaundice
  • Gynecomastia
  • Asterixis

Diagnosis

• HRS is a diagnosis of exclusion.
• Investigate for other potential causes of renal failure (sepsis, shock, nephrotoxic agents).
• Laboratory evaluation shows renal injury with prerenal azotemia.
  • ↑ Serum creatinine > 1,5 mg/dL (> 133 μmol/L)
  • ↑ BUN (blood urea nitrogen):creatinine (Cr) ratio (> 20:1)
  • No or minimal proteinuria
  • Very low urine sodium (< 10–15 mEq/dL)
  • Fractional excretion of sodium (FENa) < 1%

Management

The goal of therapy is improvement in liver function.

• Liver transplant is the only curative treatment.
• Treat any acute causes of liver failure.
• Transjugular intrahepatic portosystemic shunt (TIPS) may be used as bridging therapy.
• Pharmacotherapy: 
  • Terlipressin (vasoconstriction in splanchnic region → reduces portal pressure)
  • Midodrine
  • Octreotide
  • Albumin
• Around 40% of patients with HRS and acute kidney failure do not respond to treatment.

Differential Diagnosis

Pre-renal failure: presents with similar laboratory findings (↑ serum creatinine and ↑BUN:Cr ratio) and similar urine findings (low sodium excretion in urine). Hepatorenal syndrome can be differentiated from pre-renal failure through an IV fluid challenge. Giving fluids improves pre-renal failure but not HRS.