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For further information, see CMDT Part 16-11: Cirrhosis

Key Features

  • Characterized by

    • Azotemia (increase in serum creatinine level > 0.3 mg/dL [26.5 mcmol/L]) within 48 hours or by ≥ 50% from baseline within the previous 7 days in the absence of current or recent nephrotoxic drug use

    • Macroscopic signs of structural kidney injury

    • Shock

    • Failure of kidney function to improve following 2 days of diuretic withdrawal and volume expansion with albumin, 1 g/kg up to a maximum of 100 g/day

  • Diagnosed when other causes of acute kidney injury (AKI) (including prerenal azotemia and acute tubular necrosis) have been excluded in the setting of end-stage liver disease

Clinical Findings

  • Often precipitated by an acute decrease in cardiac output

  • Pathogenesis involves intense renal vasoconstriction

  • Histologically, the kidneys are normal

  • Acute kidney injury-hepatorenal syndrome (formerly type 1 HRS): serum creatinine doubles to a level > 2.5 mg/dL (208.25 mcmol/L) or the creatinine clearance halves to < 20 mL/min (0.34 mL/s/1.73 m2 body surface area [BSA]) in less than 2 weeks

  • Chronic kidney disease-hepatorenal syndrome (formerly type 2 HRS): chronic and slowly progressive


  • Azotemia, hyponatremia, oliguria, low urinary sodium concentration are typical features

  • Urinary neutrophil gelatinase-associated lipocalin levels (normal, 20 ng/mL) and other biomarkers may help distinguish hepatorenal syndrome (105 ng/mL) from CKD (50 ng/mL) and other causes of AKI (325 ng/mL)


  • In addition to discontinuation of diuretics, clinical improvement and an increase in short-term survival may follow intravenous infusion of albumin in combination with one of the following vasoconstrictor regimens for 7–14 days:

    • Intravenous terlipressin (not yet available in the United States but recommended for approval by an FDA Advisory Committee in 2020 and the preferred agent where available)

    • Intravenous norepinephrine

    • Oral midodrine plus subcutaneous or intravenous octreotide

  • Oral midodrine, 7.5 mg three times daily, added to diuretics, to increase blood pressure has also been reported to convert refractory ascites to diuretic-sensitive ascites

  • Survival benefit has occurred with the molecular adsorbent recirculating system (MARS), a modified dialysis method that selectively removes albumin-bound substances

  • Improvement may also follow TIPS placement

  • Liver transplantation is treatment of choice, but many patients die before a donor liver can be obtained

  • Survival after 1 year is reported to be predicted by the combination of a serum bilirubin level < 3 mg/dL (< 50 mcmol/L) and a platelet count > 75,000/mcL (> 75 × 109/L)

  • Type 1 hepatorenal syndrome is often irreversible in patients with a systemic infection

  • Continuous venovenous hemofiltration and hemodialysis are of uncertain value

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