From the Guidelines
Hepatorenal syndrome (HRS) in liver cirrhosis is a severe complication characterized by kidney failure due to intense renal vasoconstriction without structural kidney damage, with the most recent evidence suggesting that the pathophysiology involves extreme splanchnic vasodilation resulting in low effective arterial blood volume, with ensuing activation of vasoactive systems leading to renal vasoconstriction and decreases in renal blood flow 1. The pathophysiology of HRS involves several key mechanisms, including:
- Portal hypertension leading to splanchnic vasodilation, which reduces effective arterial blood volume
- Activation of compensatory mechanisms, including the renin-angiotensin-aldosterone system, sympathetic nervous system, and antidiuretic hormone release
- Extreme renal vasoconstriction while maintaining vasodilation in the splanchnic circulation, resulting in decreased renal blood flow and glomerular filtration rate
- Bacterial translocation from the gut, releasing endotoxins that stimulate nitric oxide production, worsening splanchnic vasodilation
- Cardiac dysfunction in cirrhosis (cirrhotic cardiomyopathy) further compromising renal perfusion The most recent and highest quality study, published in 2024, highlights the importance of volume expansion with albumin in patients with cirrhosis and ascites presenting with acute kidney injury (AKI) 1. Key points to consider in the management of HRS include:
- Albumin infusion as the volume expander of choice in hospitalized patients with cirrhosis and ascites presenting with AKI
- Vasoconstrictors, such as terlipressin or norepinephrine, in combination with albumin, as the first-line treatment for HRS-AKI
- Addressing precipitating factors, such as infections or gastrointestinal bleeding
- Liver transplantation as the definitive treatment, addressing the underlying cause of the pathophysiological cascade It is essential to note that the optimal dose of albumin used for HRS-AKI treatment is not established, and dosing varies considerably between studies, with some evidence suggesting a dose-dependent effect on both survival and complications in patients with cirrhosis with acute renal failure 1.
From the Research
Pathophysiology of Hepatorenal Syndrome (HRS)
- Hepatorenal Syndrome (HRS) is a reversible functional renal impairment that occurs in patients with advanced liver cirrhosis or those with fulminant hepatic failure 2.
- The pathophysiology of HRS involves a decrease in effective arterial blood volume, leading to renal vasoconstriction and a subsequent decrease in renal perfusion 3, 4.
- Inflammation also plays a significant role in the pathophysiology of renal dysfunction in cirrhosis, in addition to hemodynamic changes 5.
- The onset of HRS is a progressive process rather than a suddenly arising phenomenon, and it is characterized by a sudden onset acute renal failure and a rapid deterioration of other organ functions in Type 1 HRS, and slow and progressive worsening of renal functions due to cirrhosis and portal hypertension in Type 2 HRS 4.
Key Factors Contributing to HRS
- Advanced liver cirrhosis or fulminant hepatic failure 2, 6
- Decreased effective arterial blood volume 3, 4
- Inflammation 5
- Portal hypertension 4
- Refractory ascites 4
Diagnosis and Treatment
- HRS is diagnosed by the exclusion of other causes of acute kidney injury in cirrhotic patients, as there are no specific tests for HRS diagnosis 4.
- The combination of terlipressin and albumin is a common treatment for HRS, which can improve renal function and bridge patients to liver transplantation 2, 5, 4.
- Liver transplantation is the definitive treatment for HRS, and it can correct many of the pathophysiological abnormalities associated with HRS 3, 4.