From the Guidelines
Hepatorenal syndrome (HRS) is a severe complication of advanced liver disease characterized by kidney failure in patients with cirrhosis without another identifiable cause of kidney injury, and the first-line therapy is terlipressin (1-2mg IV every 6 hours) plus albumin, which has been shown to improve renal function and reduce mortality in patients with HRS 1.
Definition and Pathophysiology
HRS occurs due to extreme vasoconstriction of the renal arteries while systemic circulation is vasodilated, leading to reduced kidney perfusion 1. This results in a decrease in glomerular filtration rate (GFR) and an increase in serum creatinine levels.
Treatment
The treatment of HRS focuses on improving circulatory function with vasoconstrictors combined with albumin 1.
- Terlipressin is the preferred vasoconstrictor, and it is usually administered as intravenous bolus doses at 1–2 mg every 6 hours for up to 14 days 1.
- Albumin is crucial as it expands plasma volume and improves cardiac output 1.
- Patients should have diuretics discontinued, nephrotoxic medications avoided, and be evaluated for liver transplantation, which is the definitive treatment 1.
Alternative Therapies
In regions where terlipressin is unavailable, norepinephrine (0.5-3mg/hour) with albumin or midodrine (7.5-12.5mg orally three times daily) plus octreotide (100-200mcg subcutaneously three times daily) with albumin can be used 1.
- Norepinephrine has been shown to improve renal function in 39%–70% of patients, similar to that observed in the terlipressin arm 1.
Prognosis and Outcomes
Without treatment, HRS carries a poor prognosis with high mortality rates 1.
- Early recognition and prompt intervention are essential to improve outcomes in these critically ill patients 1.
- Even small reductions in serum creatinine with treatment are beneficial, and every 1-mg/dL drop in serum creatinine is associated with a 27% reduction in the relative risk for mortality 1.
From the Research
Definition and Pathogenesis of Hepatorenal Syndrome (HRS)
- Hepatorenal syndrome (HRS) is a severe complication that often occurs in patients with cirrhosis and ascites, characterized by renal failure, changes in systemic blood pressure, and increased activity of endogenous vasoactive systems 2, 3.
- The pathogenesis of HRS is the result of an extreme underfilling of the arterial circulation secondary to an arterial vasodilation located in the splanchnic circulation, triggering a compensatory response with activation of vasoconstrictor systems 2, 3.
- HRS may develop in two clinical types: as an acute and rapidly progressive renal failure (AKI-HRS) or as chronic and not progressive renal failure (CKD-HRS) 2.
Diagnosis and Prognosis of HRS
- The diagnosis of HRS is based on established diagnostic criteria aimed at excluding nonfunctional causes of renal failure 3.
- The prognosis of patients with HRS is very poor, with a high mortality rate if left untreated 2, 3.
- Liver transplantation is the best option in selected patients, but it is not always applicable due to the short survival expectancy and donor shortage 3.
Treatment of HRS
- Pharmacological therapies based on the use of vasoconstrictor drugs (such as terlipressin, midodrine, octreotide, or noradrenaline) are the most promising in aims of successfully offering a bridge to liver transplantation 2, 3.
- Terlipressin plus albumin has been shown to improve renal function in almost 35-45% of patients with AKI-HRS, as well as to improve short-term survival in these patients 2.
- α-Adrenergic drugs, such as intravenous norepinephrine or oral midodrine plus subcutaneous octreotide, administered with albumin have also been used in the treatment of AKI-HRS, with promising results 2.
- Albumin plus noradrenaline had fewer numbers of adverse events per participant compared to albumin plus terlipressin 4.
- Response to therapy is associated with improved survival, with median overall survival significantly better in patients with response to terlipressin than in patients with non-response 5.