Clinical Pearls & Morning Reports
Published February 22, 2023
Acute kidney injury (AKI) is a common condition in patients with cirrhosis. It occurs in up to 50% of hospitalized patients with cirrhosis and in 58% of such patients in the intensive care unit. Read the NEJM Review Article here.
Q: How common is the hepatorenal syndrome in patients with cirrhosis?
A: A unique cause of AKI due to renal hypoperfusion in patients with cirrhosis is the hepatorenal syndrome (HRS), which is the result of renal vasoconstriction. HRS accounts for approximately 15 to 20% of cases of AKI in patients with cirrhosis. Patients with cirrhosis who have ascites, particularly those with refractory ascites, are at the highest risk not only for the development of AKI but also for its most severe clinical form, HRS-AKI.
Q: Why are patients with cirrhosis susceptible to AKI?
A: Patients with cirrhosis, particularly those with ascites, have an increased susceptibility to AKI because of the hemodynamic alterations that result from portal hypertension. The initial mechanism in the pathogenesis of portal hypertension is increased intrahepatic resistance due to distortion of the liver architecture (fibrosis and nodules) and an increase in intrahepatic vascular tone. Subsequent activation of vasodilators in the splanchnic circulation leads to progressive splanchnic and systemic vasodilatation. Increased translocation of bacteria and bacterial products due to intestinal dysbiosis, bacterial overgrowth, and altered tight-junction proteins contributes further to vasodilatation, resulting in a reduction in the effective arterial blood volume that will activate the neurohumoral systems (the renin–angiotensin–aldosterone, sympathetic, and arginine–vasopressin systems) leading to sodium and water retention and ascites formation. In advanced stages of cirrhosis, progressive vasodilatation leads to more avid retention of sodium and water, resulting in refractory ascites and dilutional hyponatremia, respectively.
A: With progressive vasodilatation, vasoconstrictive substances (mainly renin and angiotensin II) are released, resulting in renal vasoconstriction and decreased renal blood flow. In addition, a relative decrease in cardiac output in this high-output state of cardiac failure (so-called cirrhotic cardiomyopathy) may further contribute to decreased renal perfusion. The reduced renal blood flow results in a decrease in the glomerular filtration rate and a prerenal type of kidney injury that does not respond to volume expansion — that is, HRS-AKI. Renal vasoconstriction in patients with cirrhosis is not countered by the release of vasodilatory substances (e.g., prostaglandins) because of a decrease in their production, and local release of vasoconstrictors such as endothelin. Although HRS-AKI can occur in the absence of a precipitating factor, it is more commonly precipitated by factors that cause a decrease in effective arterial blood volume. These factors include rapid fluid loss (e.g., excessive diuresis or gastrointestinal bleeding), worsening vasodilatation induced by drugs (e.g., angiotensin-converting–enzyme inhibitors), and a systemic inflammatory response (e.g., infection).
A: The mainstay of pharmacologic management of HRS-AKI is the use of vasoconstrictors combined with intravenous albumin. Vasoconstrictors have not been shown to improve survival, so their use should be considered a bridge to transplantation rather than a cure for HRS-AKI. Terlipressin, a vasopressin analogue, is the most common vasoconstrictor used worldwide, and both U.S. and European guidelines recommend it as a first-line agent for HRS-AKI.