Hepatorenal Syndrome

Hepatorenal syndrome (HRS) is functional renal failure in advanced cirrhosis or acute liver failure from intense renal vasoconstriction, with structurally normal kidneys.

• Occurs in about 10% of hospitalised patients with cirrhosis and ascites, and 40% at 5 years of ascites.
• Mechanism: splanchnic vasodilatation, effective hypovolaemia, activation of renin angiotensin and sympathetic systems, and reduced cardiac output.
• HRS AKI (formerly type 1): AKI stage 1B or higher, rapid, often triggered by spontaneous bacterial peritonitis, GI bleeding, large paracentesis without albumin, or diuretics. Median survival without treatment 2 weeks.
• HRS NAKI/CKD (formerly type 2): slower decline with diuretic resistant ascites, survival about 6 months.
• Diagnosis is by exclusion of other causes.

• Oliguria, rising creatinine, ascites, jaundice, hypotension, hyponatraemia.
• Precipitants: sepsis, bleeding, vomiting, diarrhoea, nephrotoxins (NSAIDs, aminoglycosides, contrast).
• Encephalopathy and coagulopathy in advanced liver failure.
• Low urinary sodium (below 10 mmol/L) and bland sediment.

HRS AKI criteria

• Cirrhosis with ascites.
• Rise in creatinine of 0.3 mg/dL or more in 48 hours, or 50% over baseline in 7 days.
• No response after 2 days of diuretic withdrawal and albumin 1 g/kg/day.
• No shock, no nephrotoxic drugs, and no structural kidney disease (proteinuria under 500 mg/day, microhaematuria under 50 red cells per field, normal ultrasound).
• Urinary sodium under 10 mmol/L, bland sediment. NGAL may help to separate acute tubular necrosis.
• Investigate precipitants: diagnostic paracentesis, blood and urine cultures, chest radiograph, endoscopy.

• Stop diuretics, beta blockers and nephrotoxins. Treat infection promptly.
• Volume expansion with albumin 1 g/kg (maximum 100 g) on day 1, then 20 to 40 g daily.
• Vasoconstrictors with albumin:
  • Terlipressin 0.85 mg IV every 6 hours (increase to 1.7 mg every 6 hours at day 3 if creatinine falls less than 30%) or continuous infusion 2 mg/day up to 12 mg/day, for up to 14 days. Contraindicated with hypoxia (SpO2 under 90%), volume overload, or ACLF grade 3. Monitor for ischaemia and respiratory failure.
  • Norepinephrine infusion 0.5 to 3 mg/h in ICU to raise mean arterial pressure by 10 mmHg.
  • Midodrine 7.5 to 15 mg three times daily with octreotide 100 to 200 micrograms SC three times daily if terlipressin unavailable (less effective).
• Response is creatinine below 1.5 mg/dL (or return to within 0.3 of baseline).
• TIPS for selected HRS NAKI. Renal replacement therapy as a bridge to transplantation.
• Liver transplantation is definitive. Simultaneous liver kidney transplant if dialysis is needed for 6 weeks or more.
• Prevention: albumin with spontaneous bacterial peritonitis (1.5 g/kg day 1, 1 g/kg day 3), albumin 6 to 8 g per litre after large volume paracentesis, norfloxacin prophylaxis, avoid NSAIDs.