Hepatorenal syndrome

Introduction

Hepatorenal syndrome (HRS) is a functional renal failure that occurs in patients with advanced liver disease, most commonly cirrhosis with ascites. It is characterised by reduced kidney function in the absence of structural kidney disease, hypovolaemia, or nephrotoxic injury. HRS is a diagnosis of exclusion and carries a high mortality rate if left untreated.

Peak Incidence

• Most commonly affects individuals aged 40 to 80 years, particularly those with decompensated cirrhosis and ascites.

Pathophysiology

• Cirrhosis leads to splanchnic vasodilation and reduced effective circulating volume, activating the renin-angiotensin-aldosterone system (RAAS), sympathetic nervous system, and antidiuretic hormone (ADH).
• This causes intense renal vasoconstriction and reduced renal perfusion, despite normal kidney histology.
• The result is a progressive decline in glomerular filtration rate (GFR), leading to renal failure.

Symptoms

• Progressive oliguria (reduced urine output)
• Fatigue and generalised weakness
• Nausea and vomiting
• Abdominal discomfort, often from tense ascites
• Confusion – may be due to hepatic encephalopathy

Signs

• Hypotension
• Tachycardia
• Jaundice
• Ascites
• Peripheral oedema
• Asterixis – if hepatic encephalopathy is present
• No significant proteinuria or haematuria – helps differentiate from intrinsic renal pathology

Diagnosis

Hepatorenal syndrome is a diagnosis of exclusion. All of the following must be met:

1. Cirrhosis with ascites
2. Acute kidney injury (AKI) – based on KDIGO criteria
3. No improvement in kidney function after at least 48 hours of volume expansion with IV albumin
4. Absence of:
   • Shock
   • Recent or ongoing use of nephrotoxic drugs
   • Structural kidney disease (e.g. via renal ultrasound or urinary findings)

Complications

• End-stage renal failure
• Hyperkalaemia
• Metabolic acidosis
• Hepatic encephalopathy
• Multi-organ failure
• High mortality rate if not promptly treated

Management

First-Line Treatment

1. Vasoconstrictor therapy – counters splanchnic vasodilation:
   • Terlipressin (first-line in the UK)
   • Midodrine + Octreotide – used if terlipressin is unavailable
2. Intravenous albumin – expands plasma volume and improves renal perfusion
   • Typical dose: 1 g/kg/day (up to 100 g/day)

Supportive Measures

• Stop diuretics and nephrotoxic agents (e.g. NSAIDs, aminoglycosides)
• Treat infections, particularly spontaneous bacterial peritonitis (SBP)
• Large-volume paracentesis – accompanied by albumin replacement
• Renal replacement therapy (dialysis) – if severe or refractory renal failure develops

Definitive Treatment

• Liver transplantation – the only curative option

  • Candidates should be assessed promptly due to poor prognosis without transplant