We have known for a long time that HRS represented a spectrum of pathology and pathophysiology, and this culminated in the publication in 1996 of the new criteria for the definition of HRS by the International Ascites Club of type 1 HRS and type 2 HRS.1 Without going into the definitions,

in essence type 1 HRS is the rapid onset of renal failure that occurs in patients with rapid decompensation of cirrhosis due to either alcoholic hepatitis, or acute on chronic liver failure, or acute liver failure. Type 2 HRS is the type of renal impairment observed in patients with refractory ascites, with renal function fluctuating over a relatively long period of time. This definition was born out of necessity, mainly to facilitate research check details in the area since, prior to this date, patients tended to be clumped together when it was clear that clinically and presumably their underlying pathophysiology were different. ABT 263 While these definitions have helped us move on in terms of identifying mechanisms, the definitions have by virtue of their criteria probably held us back, by identifying patients late, and with relatively advanced renal

failure. Thus, the definitions involve absolute serum creatinine values which we now know are inappropriate. Thus, a serum creatinine in a heavily built black muscular man are treated the same as an emaciated white female with advanced alcoholic liver disease. This definition bit us back when two clinical trials of terlipressin in HRS showed a response rate to treatment of 34%-40%,2, 3 probably because patients were randomized too late for true efficacy. We are now seeing articles that state predictability of response to terlipressin is determined by serum creatinine.4 Another way of putting this is that patients with early HRS respond better to treatment than patients

with advanced kidney failure. In many ways this is “kind of obvious,” so we need new criteria that can be adapted to individual patients. This was also recognized in the working party report of Wong et al.5 The development of HRS is due to four main factors. These are: (1) altered systemic hemodynamics with vasodilatation and lowering of arterial pressure; (2) activation of the sympathetic nervous system, click here which alters renal autoregulation such that renal blood flow becomes more dependent on arterial pressure; (3) a terminal decline in cardiac function due to cirrhotic cardiomyopathy, which renders patients unable to maintain an adequate cardiac output as they decompensate; and (4) increased circulating or intrarenal vasoactive mediators, the role of which remain unknown. Importantly, the role of each of these factors probably varies from patient to patient. The advent of the new definition of acute kidney injury (AKI) by the AKI network has led to a reevaluation and proposed new definitions for HRS.5 What is well recognized by all is that current criteria for HRS recognize and treat patients too late.