Hepatorenal Syndrome (HRS)

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 < 2 weeks

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

Diagnosis

• Typical features

  • Azotemia

  • Hyponatremia

  • Oliguria

  • Low urinary sodium concentration

• 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)

Treatment

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

  • Intravenous terlipressin

    • Not yet approved by the US FDA, which in 2020 requested more information regarding its risk-benefit profile

    • Remains the preferred agent where available

    • However, terlipressin is associated with serious adverse events, including respiratory failure

  • Intravenous norepinephrine plus intravenous albumin 1 g/kg on day 1 followed by 40–50 g/day for the duration of therapy

  • Oral midodrine plus subcutaneous or intravenous octreotide is less effective than terlipressin

• 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 in kidney function 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