How to manage hepatorenal syndrome (HRS)?

From the Guidelines

Management of hepatorenal syndrome (HRS) requires a multifaceted approach focusing on treating the underlying liver disease while supporting kidney function, with the first-line treatment involving vasoconstrictor therapy with terlipressin (0.5-2 mg IV every 4-6 hours) combined with albumin (20-40g/day), as recommended by the most recent and highest quality study 1. The treatment of HRS aims to improve renal perfusion by counteracting the splanchnic vasodilation and systemic vasoconstriction characteristic of HRS, thereby restoring effective arterial blood volume and improving kidney function while addressing the underlying liver disease. Some key points to consider in the management of HRS include:

• The use of terlipressin, a vasopressin analog, as the first-line vasoconstrictor therapy, with a response rate of 64-76% 1
• The importance of albumin infusion, which should be initiated at 1 g/kg on day one, followed by 20-40 g daily, to improve the efficacy of treatment on circulatory function 1
• The potential use of norepinephrine (0.5-3 mg/hour) or midodrine (7.5-12.5 mg orally three times daily) plus octreotide (100-200 mcg subcutaneously three times daily) as alternative vasoconstrictor therapies if terlipressin is unavailable 1
• The need for careful fluid management, restricting sodium (<2 g/day) while maintaining adequate intravascular volume, and avoiding diuretics and nephrotoxic medications 1
• The potential requirement for renal replacement therapy as a bridge to liver transplantation, which is the definitive treatment for HRS 1 It is essential to prioritize the single most recent and highest quality study, which in this case is 1, to guide the management of HRS and ensure the best possible outcomes for patients.

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).

• Management of hepatorenal syndrome with terlipressin involves increasing renal blood flow by reducing portal hypertension and increasing mean arterial pressure (MAP) 2.
• The mechanism of action of terlipressin is as a synthetic vasopressin analogue with selectivity for vasopressin V1 receptors, which helps to reduce portal hypertension and increase effective arterial volume.
• Administration of terlipressin has been shown to increase diastolic, systolic, and mean arterial pressure (MAP) and decrease heart rate in patients with hepatorenal syndrome type 1 (HRS-1) 2.

From the Research

Management of Hepatorenal Syndrome

The management of hepatorenal syndrome (HRS) involves various treatment options, including:

• Terlipressin plus albumin: This combination has been shown to be effective in improving renal function in patients with HRS 3, 4.
• Midodrine and octreotide plus albumin: This combination is used as an alternative treatment for HRS, especially in cases where terlipressin is not available 3, 5.
• Transjugular intrahepatic portosystemic stent shunt (TIPS): TIPS can be effective in improving renal function in selected patients with type 1 HRS, especially after improvement with midodrine, octreotide, and albumin 6.

Treatment Outcomes

The outcomes of these treatments have been studied in various clinical trials, with results showing:

• Terlipressin plus albumin is significantly more effective than midodrine and octreotide plus albumin in improving renal function in patients with HRS 3.
• The combination of octreotide, midodrine, and albumin improves survival in patients with type 1 and type 2 HRS 5.
• TIPS can improve renal function and sodium excretion in patients with type 1 HRS, especially after improvement with midodrine, octreotide, and albumin 6.
• Pre-transplant treatment of HRS with triple therapy (octreotide, midodrine, and albumin) is not associated with additional benefit in glomerular filtration rate after liver transplantation 7.

Key Considerations

When managing HRS, it is essential to consider the following:

• The type of HRS (type 1 or type 2) and the severity of renal dysfunction.
• The availability of terlipressin and the potential use of alternative treatments.
• The potential benefits and risks of TIPS and liver transplantation.
• The importance of close monitoring and adjustment of treatment as needed to optimize outcomes 3, 4, 5, 6, 7.