Epidemiology, Pathophysiology, and Management of Hepatorenal Syndrome

Abstract

Acute kidney injury (AKI) is a common presentation in patients with advanced cirrhosis hospitalized with acute decompensation. A new revised classification now divides AKI in cirrhotic patients into two broad subgroups: hepatorenal syndrome AKI (HRS AKI) and non−hepatorenal syndrome AKI (non-HRS AKI). HRS AKI represents the end-stage complication of decompensated cirrhosis with severe portal hypertension and is characterized by worsening of renal function in the absence of prerenal azotemia, nephrotoxicity, and intrinsic renal disease. Non-HRS AKI may be caused by prerenal hypoperfusion, bile acid nephropathy, nephrotoxicity, or acute parenchymal insult. There have been several mechanisms proposed to explain the pathophysiology of HRS AKI and non-HRS AKI, and a number of biomarkers have been suggested to aid in differentiation between these types of AKI and to act as prognostic indicators. The standard of care clinical management for patients with HRS AKI is to exclude other etiologies of AKI, followed by volume expansion with human albumin solution and then the introduction of vasopressors. However, some 40% of patients treated for HRS AKI fail to respond. In this review, we discuss the current and recent data about classification, pathophysiology, and management of AKI in general, with specific insight about the treatment of HRS AKI.

Cholemic Nephropathy Reloaded

“…Nevertheless, this term suggests that we know that tubular casts observed in patients with CN primarily consist of bile or biliary constituents, most likely bilirubin, while there is no information on other important biliary constituents such as phospholipids and bile acids. Other names, such as bile acid nephropathy, suggest a clarified etiopathogenesis [9][10][11][12] ; however, such an assumption would currently appear constricting and premature even in the light of some experimental evidence showing a central role for bile acids in CN. [13][14][15] In contrast, we find that the term CN is more neutral in that it indicates spill-over of biliary constituents such as bile acids and bilirubin into blood (i.e., cholemia) leading to renal dysfunction and histological changes in jaundiced patients.…”

LCAT protects against Lipoprotein‐X formation in a murine model of drug‐induced intrahepatic cholestasis

“…Furthermore, rhLCAT treatment can prevent Lp‐X formation in animal models of FLD and prevent renal damage . Acute kidney injury following a wide variety of liver diseases, including cholestasis, is also known to occur and is a common outcome in hepatorenal syndrome . In a dog model of cholestasis, Lp‐X was shown to be deposited in the glomeruli and cause renal damage but the causal role of Lp‐X in renal injury in human liver diseases requires additional studies.…”

“…18 Acute kidney injury following a wide variety of liver diseases, including cholestasis, is also known to occur 48,49 and is a common outcome in hepatorenal syndrome. 50 In a dog model of cholestasis, Lp-X was shown to be deposited in the glomeruli and cause renal damage 24,25 but the causal role of Lp-X in renal injury in human liver diseases requires additional studies. Lp-X from cholestasis has been clearly shown to cause severe xanthomas, which can be quite disfiguring, particularly in Allagile syndrome 12 and is due to the uptake of Lp-X by dermal macrophages.…”

Frequency of Hepatorenal Syndrome Among Patients With Cirrhosis and Outcome After Treatment

“…The complications of cirrhosis, such as hepatic encephalopathy, upper gastrointestinal bleed, HRS and hepatopulmonary syndrome, cause a high mortality rate of the disease. Hepatorenal syndrome (HRS) is a complication describing functionally deteriorating kidneys in liver failure (either acute or chronic) [ 3 ].…”