Key Facts

HRS is a diagnosis of exclusion in patients with severe liver disease. Early recognition and treatment with terlipressin improve short-term survival and may bridge patients to liver transplantation.

Epidemiology

• Develops in ~40% of patients with cirrhosis and ascites within 5 years
• Annual incidence: 8-10% of hospitalised patients with ascites
• Most common precipitant: spontaneous bacterial peritonitis (SBP)

Aetiology

• Advanced cirrhosis (most common), acute liver failure, acute-on-chronic liver failure
• Precipitants: SBP, large-volume paracentesis without albumin replacement, GI haemorrhage, sepsis, nephrotoxins

Pathophysiology

• Portal hypertension → splanchnic vasodilation (NO, prostacyclin-mediated)
• Reduced effective arterial blood volume → baroreceptor-mediated activation of RAAS, sympathetic nervous system, and ADH
• Intense renal vasoconstriction → reduced renal blood flow and GFR
• Kidneys are structurally normal; HRS kidneys function normally when transplanted into non-cirrhotic recipients
• Cardiac output eventually becomes insufficient (cirrhotic cardiomyopathy) → further renal hypoperfusion

HRS-AKI (Type 1)

• Rapid deterioration in renal function (doubling of creatinine within 2 weeks)
• Often precipitated by SBP or GI bleed
• Oliguria
• Usually in the context of acute decompensation

HRS-CKD (Type 2)

• Gradual decline in renal function
• Refractory ascites is the dominant feature
• Better short-term prognosis than HRS-AKI

Context

• Jaundice, ascites, spider naevi, encephalopathy
• Hypotension, low MAP
• Peripheral vasodilation

Red Flags

• SBP (abdominal pain, fever, confusion) → diagnostic paracentesis, start empirical antibiotics
• Acute variceal haemorrhage → splanchnic hypoperfusion
• Urine sodium <10 mmol/L in the context of cirrhosis and rising creatinine

Diagnostic Criteria (ICA 2015)

• Cirrhosis with ascites
• AKI (rise in creatinine ≥26.5 µmol/L within 48 hours or ≥50% from baseline within 7 days)
• No improvement after 48 hours of diuretic withdrawal and volume expansion with IV albumin 1g/kg/day (max 100g/day)
• No shock
• No nephrotoxic drugs
• No structural kidney disease (no proteinuria >500mg/day, no haematuria, normal renal USS)

Bloods

• U&Es: rising creatinine, low sodium (dilutional hyponatraemia)
• LFTs: deranged (advanced liver disease)
• Albumin: low
• FBC: thrombocytopenia (portal hypertension), anaemia
• Coagulation: prolonged PT/INR
• Urine sodium: <10 mmol/L (avid sodium retention)

Imaging

• Renal USS: normal kidneys, no obstruction
• Ascitic tap: if SBP suspected (neutrophil count >250/mm³)

Special Tests

• Volume challenge: IV albumin 1g/kg/day for 48 hours to exclude pre-renal cause
• Urine sediment: bland (no casts, no haematuria)

Pharmacological

• Terlipressin 1mg IV QDS (titrate to 2mg QDS if no response by day 3) + IV albumin 20-40g/day
  • CONFIRM trial: terlipressin improved verified HRS reversal
  • Continue until creatinine <133 µmol/L or max 14 days
  • Monitor for cardiac ischaemia, peripheral vasoconstriction, fluid overload
• Alternative: noradrenaline infusion (0.5-3mg/hr) + albumin – used in ICU setting (NICE accepts as equivalent)
• Midodrine (alpha-1 agonist) + octreotide: oral alternative if terlipressin unavailable; less effective

Supportive

• Treat precipitant: antibiotics for SBP (IV ceftriaxone 1g OD or co-amoxiclav), manage GI bleeding
• Avoid nephrotoxins: NSAIDs, aminoglycosides
• Monitor: fluid balance, daily U&Es, MAP

Definitive Treatment

• Liver transplantation: only curative treatment; renal function often recovers post-transplant
• TIPS (transjugular intrahepatic portosystemic shunt): may improve renal function as bridge to transplant; contraindicated if severe encephalopathy
• Combined liver-kidney transplant: if prolonged dialysis (>12 weeks)

Referral

• All HRS → hepatology/liver transplant team
• Consider ICU if haemodynamic support needed
• Dialysis as bridge to transplant only (not as standalone treatment for HRS)

• HRS-AKI without treatment: median survival ~2 weeks
• HRS-AKI with terlipressin + albumin: reversal in 40-50%; improved short-term survival
• HRS-CKD: median survival ~6 months
• Post-liver transplant: renal function recovers in majority; 5-year survival 60-70%
• Without transplant: HRS is uniformly fatal
• MELD score (Model for End-Stage Liver Disease): incorporates creatinine; predicts mortality and transplant priority

HRS-AKI vs HRS-CKD

SBP Prophylaxis to Prevent HRS