News in pathophysiology, definition and classification of hepatorenal syndrome: A step beyond the International Club of Ascites (ICA) consensus document

Abstract

Renal dysfunction is a common, life-threatening complication occurring in patients with liver disease. Hepatorenal syndrome (HRS) has been defined as a purely "functional" type of renal failure that often occurs in patients with cirrhosis in the setting of marked abnormalities in arterial circulation, as well as overactivity of the endogenous vasoactive systems.^4,5 In 2007, the International Club of Ascites (ICA) classified HRS into types 1 and 2 (HRS-1 and HRS-2).⁵ HRS-1 is characterised by a rapid deterioration of renal function that often occurs because of a precipitating event, while HRS-2 is a moderate and stable or slowly progressive renal dysfunction that often occurs without an obvious precipitant. Clinically, HRS-1 is characterised by acute renal failure while HRS-2 is mainly characterised by refractory ascites. Nevertheless, after these two entities were first described, new concepts, definitions, and diagnostic criteria have been developed by nephrologists for renal dysfunction in the general population and hospitalised patients. In particular, the definitions and characterisation of acute kidney injury (AKI), acute kidney disease and chronic kidney disease have been introduced/refined.⁶ Accordingly, a debate among hepatologists of the ICA led to a complete revision of the nomenclature and diagnosistic criteria for HRS-1, which was renamed HRS-AKI.⁷ Additionally, over recent years, greater granularity has been gained regarding the pathogenesis of HRS; it is now increasingly recognised that it is not a purely "functional" entity with haemodynamic derangements, but that systemic inflammation, oxidative stress and bile salt-related tubular damage may contribute significantly to its development. That is, HRS has an additional structural component that would not only make traditional diagnostic criteria less reliable, but would explain the lack of response to pharmacological treatment with vasoconstrictors plus albumin that correlates with a progressive increase in inflammation. Because classification, nomenclature, diagnostic criteria and pathogenic theories have evolved over the years since the traditional classification of HRS-1 and HRS-2 was first described, it was considered that all these novel aspects be reviewed and summarised in a position paper. The aim of this position paper authored by two hepatologists (members of ICA) and two nephrologists involved in the study of renal dysfunction in cirrhosis, is to complete the re-classification of HRS initiated by the ICA in 2012 and to provide an update on the definition, classification, diagnosis, pathophysiology and treatment of HRS.

Keywords: Acute Kidney Disease; Acute Liver Failure; Acute kidney Injury; Acute on chronic liver failure; Albumin; Biomarkers; Chronic Kidney Disease; Cirrhosis; Liver Disease; Liver transplantation; MELD; Midodrine; NGAL; Noradrenaline; Portal Hypertension; Serum creatinine; Simultaneous liver Kidney Transplantation; Systemic Inflammation; Terlipressin.