Hepatorenal syndrome

Hepatorenal syndrome (HRS) refers to a unique type of kidney injury that occurs in patients with cirrhosis and ascites. The pathophysiology is not well understood but is likely due to splanchnic vasodilation in the setting of portal hypertension. HRS may develop rapidly in the case of HRS acute kidney injury (HRS-AKI) or gradually in the case of HRS non-acute kidney injury (HRS-NAKI). It is a diagnosis of exclusion and requires the elimination of other potential etiologies, including hypovolemia. A liver transplant is the only curative treatment, but it may be mitigated pharmacologically with vasoconstrictors and albumin.

• A unique phenotype of kidney injury in patients with cirrhosis and ascites in the absence of hypovolemia or other kidney pathology. It is further split into: ^[1][2]
  • HRS-acute kidney injury (HRS-AKI): acute kidney injury in patients with cirrhosis (see “Diagnostic criteria for HRS-NAKI” below); formerly known as type 1 HRS
  • HRS-non-acute kidney injury (HRS-NAKI): functional kidney injury in patients with cirrhosis not meeting the criteria for HRS-AKI; formerly known as type 2 HRS

• AKI is present in approximately 30–50% of hospitalized patients with decompensated cirrhosis and ascites ^[1]

Epidemiological data refers to the US, unless otherwise specified.

• Complication of liver failure, especially cirrhosis
• The exact pathomechanisms are not completely understood: Cirrhosis/portal hypertension → ↑ splanchnic vasodilators (e.g., nitric oxide) → ↓ arterial blood flow → activation of RAAS → renal vasoconstriction → ↓ GFR ^[2]
• Risk factors/triggers may include:
  • Drainage of large volume ascites (without concurrent albumin administration) ^[3]
  • Gastrointestinal bleeding
  • Forced diuresis
  • Excess use of laxatives (lactulose)
  • Infections, e.g., spontaneous bacterial peritonitis

• Ranging from oliguria up to anuria with progressive kidney failure
• See also “Cirrhosis” and “Decompensated cirrhosis.”
• Hypotension and wide pulse pressure

Hepatorenal syndrome (HRS) is a diagnosis of exclusion. It is diagnosed based on the presence of renal impairment in patients with cirrhosis after other potential causes of renal impairment have been ruled out. ^[1][3]

• Initial evaluation
  • Clinical evaluation: Rule out shock, hypovolemia, and nephrotoxic agent intake.
  • Laboratory studies
    • Creatinine
    • Urine studies: urinalysis, urine sediment, fractional excretion of sodium or urea ^[3][4]
    • Imaging: Abdominal ultrasound to assess for obstruction
• Diagnostic criteria for HRS-AKI ^[1][4][5]
  • Presence of cirrhosis with ascites
  • Diagnosis of AKI according to the following criteria: ^[4]
    • An increase in serum creatinine of ≥ 0.3 mg/dL within 48 hours or to ≥ 1.5 times baseline within a 7-day period
    • And/or urine output ≤ 0.5 mL/kg for ≥ 6 hours
  • No improvement after two consecutive days of albumin infusions and diuretic withdrawal
  • Absence of shock
  • No current or recent nephrotoxic agents
  • Absence of signs of structural kidney disease

Treatment for HRS-AKI should always be combined with adequate management for cirrhosis, and a multidisciplinary team should be involved as soon as possible. Data on effective treatments for HRS-NAKI is lacking. ^[1]

Pharmacotherapy for HRS-AKI ^[1]

• Preferred: vasoconstrictor (either terlipressin OR norepinephrine) PLUS albumin
• Alternative: combination of midodrine; PLUS octreotide

Surgical or interventional options ^[1]

• Renal replacement therapy (mainly hemodialysis) ^[1]
• A liver transplant is the only curative option.
• TIPS placement is not routinely recommended. ^[1][3]

Prevention

• General measures: prevention of GI bleeding and bacterial infections, avoidance of large-volume paracentesis without concurrent albumin administration
• Specific measures: IV albumin with antibiotics reduces the risk of patients with spontaneous bacterial peritonitis developing HRS-AKI.

Rule out other causes of AKI and ensure the diagnostic criteria for HRS-AKI are fulfilled before initiating vasoconstrictor therapy.

Vasoconstrictor therapy is challenging and has potentially severe adverse effects (e.g., ischemia); involve specialists early.

Patients with cirrhosis and HRS can develop significant fluid retention and pulmonary edema. Therefore, administer IV fluids with caution. ^[2]