What is Hepatorenal Syndrome (HRS), a type of progressive kidney dysfunction (Impaired Renal Function) seen in individuals with severe liver disease?

From the Guidelines

Terlipressin (1 mg/4–6 h intravenous bolus) in combination with albumin should be considered the first-line therapeutic agent for type 1 hepatorenal syndrome (HRS). The aim of therapy is to improve renal function sufficiently to decrease serum creatinine to less than 133 lmol/L (1.5 mg/dl) (complete response) 1. This approach is supported by the most recent and highest quality study, which emphasizes the importance of early treatment and monitoring of patients with HRS 1.

Key Considerations

• The dose of terlipressin should be increased in a stepwise manner up to a maximum of 2 mg/4 h if serum creatinine does not decrease at least 25% after 3 days 1.
• Treatment should be discontinued within 14 days if there is no response or if serum creatinine does not decrease to less than 133 lmol/L 1.
• Patients on terlipressin need to be monitored for the development of ischemic complications such as arrhythmia, angina, and splanchnic and digital ischemia 1.
• Predictors of response to terlipressin include a baseline bilirubin of <10 mg/dL, a baseline serum creatinine of <5 mg/dL, and lower stage of acute-on-chronic liver failure 1.

Alternative Treatments

• If terlipressin is unavailable, norepinephrine (0.5-3 mg/hour) with albumin can be used as an alternative 1.
• Midodrine (7.5-12.5 mg orally three times daily) plus octreotide (100-200 mcg subcutaneously three times daily) with albumin is another alternative in settings where IV vasopressors cannot be administered 1.

Definitive Treatment

• Definitive treatment is liver transplantation, which should be considered in eligible patients as HRS carries a poor prognosis without transplantation 1.

From the Research

Definition and Pathophysiology of Hepatorenal Syndrome

• Hepatorenal syndrome (HRS) is a severe complication of end-stage cirrhosis characterized by increased splanchnic blood flow, hyperdynamic state, a state of decreased central volume, activation of vasoconstrictor systems, and extreme kidney vasoconstriction leading to decreased GFR 2.
• The pathophysiologic cascade that leads to HRS begins with pooling of blood in the splanchnic system, resulting in a decrease in effective circulating arterial volume 3.
• Systemic inflammation, a key feature of cirrhosis, contributes to the development of HRS, but the mechanisms by which it precipitates kidney circulatory changes need to be clarified 2.

Diagnosis and Treatment of Hepatorenal Syndrome

• Early diagnosis is central in the management of HRS, and recent changes in the definition of HRS help identify patients at an earlier stage 2.
• Vasoconstrictive agents (terlipressin in particular) and albumin are the first-line treatment option for HRS 2, 4, 3.
• Terlipressin plus albumin is significantly more effective than midodrine and octreotide plus albumin in improving renal function in patients with HRS 4.
• The combination of octreotide, midodrine, and albumin has shown possible benefit in improving renal function and short-term survival in patients with HRS type 1 and type 2 5.
• Transjugular intrahepatic portosystemic stent shunt (TIPS) is an effective treatment for type 1 HRS in suitable patients with cirrhosis and ascites, following the improvement of renal function with combination therapy of midodrine, octreotide, and albumin 6.

Prognosis and Liver Transplantation

• Liver transplantation is the only curative treatment of HRS 2, 3.
• Patients transplanted with HRS tend to have lower GFR compared with patients without HRS in the long term 2.
• Even in responders to treatment, early mortality rates are very high in the absence of liver transplantation 2.
• Improvement in renal function and lower baseline Model for End-Stage Liver Disease score are associated with better survival 4.