OVERVIEW

What is hepatorenal syndrome?

Hepatorenal syndrome (HRS) is a severe complication primarily characterized by renal impairment, occurring in patients with advanced liver diseases or acute liver conditions such as cirrhosis with ascites, acute liver failure, alcoholic hepatitis, or metastatic liver tumors.

Although HRS can occur in most types of severe liver disease, it is relatively rare in patients with primary biliary cholangitis.

Is hepatorenal syndrome common?

The exact incidence remains unclear, but 35%–40% of patients with end-stage liver disease and ascites may eventually develop HRS.

SYMPTOMS

What are the common manifestations of hepatorenal syndrome?

For patients with diagnosed or clinically apparent acute or chronic liver disease, the following manifestations may occur:

• Progressive increase in serum creatinine levels;
• Urine sediment examination is usually normal;
• No or minimal proteinuria (less than 500 mg/d);
• Very low sodium excretion rate (i.e., urinary sodium concentration below 10 mEq/L);
• Oliguria;

However, not all patients with hepatorenal syndrome exhibit oliguria (especially in the early stages), progressive elevation of serum creatinine levels, or benign urine sediment findings.

What are the types of hepatorenal syndrome?

Based on the rate of renal function decline, hepatorenal syndrome can be classified into the following two major types:

• Type 1 hepatorenal syndrome: Type 1 is the more severe form; it is defined as at least a doubling of serum creatinine levels (reflecting a 50% reduction in creatinine clearance) to greater than 2.5 mg/dL (221 μmol/L) within less than 2 weeks. At diagnosis, some patients with type 1 hepatorenal syndrome have a urine output of less than 400–500 mL/d.
• Type 2 hepatorenal syndrome: Type 2 involves less severe renal impairment than type 1. The main clinical feature of type 2 hepatorenal syndrome is diuretic-resistant ascites.

CAUSES

What factors can trigger the occurrence of hepatorenal syndrome?

Renal failure usually develops insidiously, but can also be induced by acute injuries such as bacterial infections or gastrointestinal bleeding.

For example, spontaneous bacterial peritonitis (SBP) can trigger progressive hepatorenal syndrome, although this is more likely to occur in patients with pre-existing renal insufficiency.

For type 1 hepatorenal syndrome caused by bacterial infections, antibiotic treatment alone typically does not improve renal function.

DIAGNOSIS

Which medical histories are closely related to the diagnosis of hepatorenal syndrome?

Previous history of hepatitis, cirrhosis, or cardiac insufficiency, current or recent use of nephrotoxic medications, and recent elevation in serum creatinine levels.

What tests are required to confirm hepatorenal syndrome?

Hepatorenal syndrome is a diagnosis of exclusion. Before diagnosing hepatorenal syndrome, other potential causes of acute or subacute kidney injury in patients with liver disease must first be ruled out.

• Liver function tests: Elevated transaminases and bilirubin indicate liver dysfunction.
• Kidney function tests: Elevated serum creatinine suggests kidney dysfunction and aids in diagnosis.
• Abdominal ultrasound: Assesses for cirrhosis, ascites, and liver disease severity; excludes renal parenchymal disease and obstructive nephropathy.
• Urinalysis: Red blood cells < 50 cells/high-power field (without catheterization) and protein excretion < 500 mg/day support the diagnosis.
• Complete blood count: Elevated white blood cells or neutrophils suggest infection.

Which diseases are easily confused with hepatorenal syndrome?

• Glomerulonephritis: Like hepatorenal syndrome, it presents with liver and kidney dysfunction. In cirrhotic patients, acute tubular necrosis may develop rapidly after aminoglycoside therapy, radiocontrast administration, sepsis, or hypotensive bleeding. Differentiation relies on acute progression and rapid creatinine elevation. Urine sediment may show red blood cells or red blood cell casts.
• Prerenal disease: In cirrhotic patients, gastrointestinal fluid loss (e.g., vomiting, diarrhea), bleeding, or diuretic/NSAID use can trigger prerenal conditions manifesting as kidney dysfunction. Discontinuing nephrotoxic drugs and fluid resuscitation without improvement in kidney function rules out prerenal disease.

TREATMENT

Which department should I visit for hepatorenal syndrome?

Seek treatment at a qualified hospital with appropriate medications in the nephrology, hepatology, or gastroenterology department. If the condition is severe, admission to the intensive care unit may be required.

How is hepatorenal syndrome treated?

• Medical treatment:
  • Vasoconstrictors combined with albumin: Vasoconstrictors include norepinephrine and terlipressin, with norepinephrine requiring close medical supervision. Vasoconstrictors can reduce vasodilation, while albumin increases effective blood volume. Combined use can improve renal function in hepatorenal syndrome patients, typically administered for 2 weeks.
  • Blood purification therapy: Continuous renal replacement therapy (CRRT) may be performed for patients unresponsive to vasoconstrictor-albumin therapy, with fluid overload, metabolic acidosis, or refractory hyperkalemia. Dialysis survival rates are generally limited by the severity of liver failure and concurrent respiratory failure.
  • Interventional therapy: Transjugular intrahepatic portosystemic shunt (TIPS) is a key treatment for portal hypertension with upper gastrointestinal bleeding or refractory ascites. Some successful cases have been reported for type 1 HRS patients, but evidence is limited, and efficacy remains uncertain. TIPS may be attempted for patients unresponsive to medical treatment.
• Surgical treatment:
  • Peritoneovenous shunting is used in rare cases. This procedure diverts ascites from the peritoneum into the internal jugular vein, reintroducing it into the vascular system. It has been employed for refractory ascites and renal failure caused by hepatorenal syndrome. The main issue is a relatively high complication rate, including disseminated intravascular coagulation (due to endotoxins or procoagulants in ascites entering the bloodstream), shunt-related infections leading to bacteremia, volume overload, variceal bleeding from increased portal pressure, and intestinal obstruction. Peritoneovenous shunting is only suitable for:
    • Specific types of ascites, such as chylous ascites.
    • Post-liver transplant patients with refractory ascites.
    • Patients with cirrhosis and diuretic-resistant ascites who are ineligible for transplant or TIPS, or who are too obese or have excessive abdominal scarring for safe paracentesis.
  • Liver transplantation: If liver failure shows no improvement after medical and blood purification therapies, early liver transplantation is necessary. For HRS patients, living-donor liver transplantation (LDLT) may be a preferable option.

Can hepatorenal syndrome cause death?

Hepatorenal syndrome is a severe complication in patients with chronic liver disease and advanced liver failure, and it is a leading cause of mortality.

Most patients die within weeks of developing renal impairment. Survival largely depends on the reversibility of liver function.

DIET & LIFESTYLE

What should patients with hepatorenal syndrome pay attention to in daily life?

• Get adequate rest and avoid physical exertion.
• Follow a low-salt, low-fat, high-quality protein, and high-energy diet.
• Abstain from alcohol.
• Maintain a healthy lifestyle and refrain from smoking.
• Learn to self-regulate when experiencing high stress or emotional tension.

PREVENTION

Can Hepatorenal Syndrome Be Prevented? How to Prevent It?

Clinically, preventing the occurrence of HRS in patients with end-stage liver disease is of great significance.

Studies have shown that administering albumin infusions in patients with spontaneous bacterial peritonitis, prophylactic antibiotic use in patients with upper gastrointestinal bleeding, and large-volume paracentesis with albumin infusion in cirrhotic patients with ascites can help prevent type 1 HRS.

• Prevention and Early Control of Bacterial Infections: Bacterial infections are a common cause of HRS in cirrhotic patients. Early control and prevention of infections help suppress inflammatory cytokine release and stabilize hemodynamics, thereby preventing HRS. Broad-spectrum antibiotics are recommended for suspected bacterial infections until culture results are negative. Additionally, administering albumin (1 g/kg body weight) for at least two consecutive days can improve perfusion and adsorb most bacterial metabolites or inflammatory factors.
• Correcting Anemia and Preventing Bleeding: Anemia can lead to renal microcirculatory ischemia and hypoxia while activating the sympathetic nervous system, exacerbating cirrhotic hyperdynamic circulation, which may trigger HRS. Therefore, preventing anemia caused by bleeding is crucial in HRS prevention.
• Avoiding Nephrotoxic Drugs: Caution should be exercised when using nephrotoxic drugs such as aminoglycosides, NSAIDs, and contrast agents in patients with cirrhosis or severe liver disease.
• Maintaining Blood Volume and Fluid-Electrolyte Balance: Patients with end-stage liver disease often have reduced peripheral vascular resistance and decreased effective blood volume. Even if supine blood pressure remains within the normal range, vigilance is required for potential shock or electrolyte imbalances that may trigger HRS.