Hepatorenal Syndrome

Hepatorenal syndrome (HRS) is a potentially reversible cause of acute kidney injury that develops secondary to liver disease. The main cause of HRS is hypovolemia, often as a result of forced diuresis or drainage of ascites. This leads to renal vasoconstriction resulting in hypoperfusion of the kidneys. Patients typically present with edema, oliguria or anuria, and ascites in the setting of acute or chronic liver injury. Hepatorenal syndrome is considered a diagnosis of exclusion. Treatment is with agents that cause systemic vasoconstriction and, therefore, improve renal perfusion. This includes octreotide and midodrine. Most cases of hepatorenal syndrome have a poor prognosis.

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Hepatorenal syndrome is associated with portal hypertension due to:

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


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


  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
Hepatorenal syndrome pathophysiology

Pathophysiology of hepatorenal syndrome

Image by Lecturio.

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
Itraconazole associated quadriparesis and edema

Lower extremity edema due to fluid retention in a patient with hepatorenal syndrome

Image: “Itraconazole associated quadriparesis and edema” by National Aspergillosis Centre, Education and Research Centre, University Hospital of South Manchester (Wythenshawe Hospital), Southmoor Road, Manchester M23 9LT, UK. License: CC BY 2.0


  • 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 (< 1015 mEq/dL)
    • Fractional excretion of sodium (FENa) < 1%


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.


  1. Amin, A. A., Alabsawy, E. I., Jalan, R., & Davenport, A. (2019). Epidemiology, pathophysiology, and management of hepatorenal syndrome. Seminars in nephrology, 39(1), 17–30.
  2. Mukhtar, A., & Dabbous, H. (2016). Modulation of splanchnic circulation: Role in perioperative management of liver transplant patients. World journal of gastroenterology, 22(4), 1582–1592. https://doi.org/10.3748/wjg.v22.i4.1582

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