What is the management of Hepatorenal Syndrome (HRS)?

From the Guidelines

Hepatorenal syndrome (HRS) management requires prompt intervention with vasoconstrictors combined with albumin as the cornerstone of treatment, with terlipressin (0.5-2 mg IV every 4-6 hours) plus albumin (20-40g/day) being the first-line therapy, as recommended by the most recent guidelines 1. The management of HRS involves several key components, including:

• Vasoconstrictor therapy to counteract splanchnic vasodilation and improve renal perfusion
• Albumin administration to expand intravascular volume and improve circulatory function
• Discontinuation of diuretics and avoidance of nephrotoxic medications to minimize further renal injury
• Maintenance of intravascular volume to support renal perfusion
• Consideration of renal replacement therapy as a bridge to liver transplantation, which remains the definitive treatment for HRS

The choice of vasoconstrictor therapy depends on availability and patient-specific factors, with terlipressin being the preferred agent due to its efficacy and safety profile, as demonstrated in several studies 1. Norepinephrine (0.5-3 mg/hour) with albumin is an effective alternative, particularly in ICU settings, while midodrine (7.5-12.5 mg orally three times daily) plus octreotide (100-200 mcg subcutaneously three times daily) with albumin can be used in patients without access to these options.

Albumin should be administered at 1 g/kg on day 1 (maximum 100g), followed by 20-40g daily, as recommended by the guidelines 1. The duration of treatment should be continued until serum creatinine improves or for up to 14 days, with regular monitoring of renal function and adjustment of therapy as needed.

Overall, the management of HRS requires a multifaceted approach that addresses the underlying pathophysiology of the disease, with the goal of improving renal perfusion, restoring effective arterial blood volume, and ultimately reducing morbidity and mortality.

From the FDA Drug Label

Terlipressin is thought to increase renal blood flow in patients with hepatorenal syndrome by reducing portal hypertension and blood circulation in portal vessels and increasing effective arterial volume and mean arterial pressure (MAP). The management of Hepatorenal Syndrome (HRS) may involve the use of terlipressin (IV), which is thought to increase renal blood flow by reducing portal hypertension and increasing mean arterial pressure (MAP) 2.

• The drug acts as a vasopressin analogue with selectivity for vasopressin V1 receptors.
• It is administered as an IV injection. The exact management protocol is not explicitly stated in the provided drug label.

From the Research

Management of Hepatorenal Syndrome (HRS)

The management of HRS involves a combination of pharmacological and non-pharmacological interventions, aiming to improve renal function and reduce the risk of mortality 3, 4, 5, 6, 7.

• Pharmacological treatments include:
  • Vasoconstrictors, such as terlipressin and midodrine, which have been shown to improve renal function and reduce mortality in HRS patients 3, 4, 5, 6
  • Albumin infusion, which is often used in combination with vasoconstrictors to improve renal function 3, 4, 5, 6, 7
• Non-pharmacological interventions include:
  • Invasive procedures such as transjugular intrahepatic portosystemic shunt (TIPS), which has been shown to be effective in improving renal function in HRS patients 3, 4, 5, 7
  • Plasma exchange, liver transplantation, and renal replacement therapy, which may also be considered in the management of HRS 3, 4, 7
  • Artificial hepatic support devices, which are important for patients who do not respond to medical treatment 7

Treatment Options

• Liver transplantation is considered the definitive treatment for HRS, particularly for patients with end-stage liver disease 3, 4, 5, 7
• Terlipressin plus albumin is a commonly used treatment regimen for HRS, and has been shown to be more effective than midodrine and octreotide plus albumin in improving renal function 6
• Midodrine and octreotide plus albumin may be used as an alternative treatment regimen in patients who do not respond to terlipressin or in countries where terlipressin is not available 4, 6

Prevention and Early Recognition

• Early recognition and prompt intervention in HRS patients is crucial, as delaying treatment can result in poorer outcomes 3
• Prevention of HRS is also important, and can be achieved through the use of albumin and pentoxifylline in patients with cirrhosis and spontaneous bacterial peritonitis or acute alcoholic hepatitis 5