What are the definitions and causes of Hepatorenal Syndrome (HRS), a type of progressive kidney dysfunction (Impaired Renal Function) in individuals with advanced liver disease?

From the Guidelines

Hepatorenal syndrome (HRS) is a serious complication of advanced liver disease characterized by rapid deterioration of kidney function without structural kidney damage, and the most recent evidence suggests that it should be treated with vasoconstrictors like terlipressin or norepinephrine combined with albumin to improve renal perfusion, as recommended by the AGA clinical practice update on the use of vasoactive drugs and intravenous albumin in cirrhosis 1. The primary cause of HRS is severe circulatory dysfunction in advanced liver disease, where splanchnic vasodilation leads to reduced effective arterial blood volume, triggering compensatory mechanisms including activation of the renin-angiotensin-aldosterone system, sympathetic nervous system, and antidiuretic hormone release, resulting in intense renal vasoconstriction and reduced kidney perfusion 1. Some key points to consider in the diagnosis and management of HRS include:

• The criteria for diagnosis of HRS in cirrhosis, which include serum creatinine >1.5 mg/dl, absence of shock, absence of hypovolemia, no current or recent treatment with nephrotoxic drugs, and absence of parenchymal renal disease 1
• The classification of HRS into two types: type 1 HRS, characterized by a rapid and progressive impairment in renal function, and type 2 HRS, characterized by a stable or less progressive impairment in renal function 1
• The use of vasoconstrictors like terlipressin or norepinephrine combined with albumin to improve renal perfusion, as recommended by the AGA clinical practice update on the use of vasoactive drugs and intravenous albumin in cirrhosis 1
• The importance of treating the underlying liver disease, discontinuing nephrotoxic drugs, addressing infections, and using vasoconstrictors to improve renal perfusion, as well as considering liver transplantation as the definitive treatment for eligible patients 1. It is also important to note that the diagnosis of HRS requires excluding other causes of acute kidney injury, and that the management of HRS should be individualized based on the patient's specific needs and circumstances, as recommended by the EASL clinical practice guidelines for the management of patients with decompensated cirrhosis 1.

From the FDA Drug Label

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From the Research

Definitions of Hepatorenal Syndrome

• Hepatorenal syndrome (HRS) is a critical and potentially life-threatening complication of advanced liver disease, including cirrhosis, characterized by the development of renal dysfunction in the absence of underlying structural kidney pathology 2.
• HRS is a form of acute kidney injury (AKI) that occurs in patients with cirrhosis, specifically those with advanced disease and ascites 3.
• The syndrome is also known as hepatorenal syndrome type of acute kidney injury (HRS-AKI), formerly referred to as type 1 hepatorenal syndrome 4, 3.

Cause of Hepatorenal Syndrome

• 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, leading to intense renal vasoconstriction 5.
• The pathophysiology of HRS involves complex interactions between systemic and renal hemodynamics, neurohormonal imbalances, and the intricate role of vasoconstrictor substances 2.
• Systemic hemodynamic changes caused by liver disease, inflammation, and damage to renal parenchyma are also thought to contribute to the development of HRS-AKI 3.
• Newly identified mechanisms involved in the development of HRS are related to the inflammatory response, conditioning the development of extrahepatic organ dysfunction in patients with cirrhosis 4.

Key Characteristics of Hepatorenal Syndrome

• HRS is characterized by functional renal failure due to renal vasoconstriction in the absence of underlying kidney pathology 5.
• The onset of HRS-AKI is marked by sudden severe renal vasoconstriction, leading to an acute reduction in glomerular filtration rate and rapid, potentially life-threatening, renal deterioration 3.
• The prognosis of patients with HRS is extremely poor, especially in those who have a rapidly progressive course 5.