Three independent risk factors for the development of HRS in cirrhotics have been identified: liver size, plasma renin activity, and serum sodium concentration.The prognosis of these patients is grim with untreated patients having an extremely short survival. The severity of liver disease (as evidenced by the MELD score) has been shown to be a determinant of outcome. Some patients without cirrhosis develop HRS, with an incidence of about 20% seen in one study of ill patients with alcoholic hepatitis. History
The first reports of kidney failure occurring in individuals with chronic liver diseases were from the late 19th century by Frerichs and Flint. However, the hepatorenal syndrome was first defined as acute kidney failure that occurred in the setting of biliary surgery. The syndrome was soon re-associated with advanced liver disease, and, in the 1950s, was clinically defined by Sherlock, Hecker, Papper, and Vessin as being associated with systemic hemodynamic abnormalities and high mortality. Hecker and Sherlock specifically identified that individuals with HRS had low urinary output, very low sodium in the urine, and no protein in the urine. Murray Epstein was the first to characterize splanchnic vasodilation and kidney vasoconstriction as the key alterations in hemodynamics in patients with the syndrome. The functional nature of the kidney impairment in HRS was crystallized by studies demonstrating that kidneys transplanted from patients with hepatorenal syndrome returned to function in the new host, leading to the hypothesis that hepatorenal syndrome was a systemic condition and not a kidney disease.
The underfill theory involves activation of the renin–angiotensin–aldosterone system, which leads to an increase in absorption of sodium from the kidney tubule (termed renal sodium avidity) mediated by aldosterone, which acts on mineralocorticoid receptors in the distal convoluted tubule. This is believed to be a key step in the pathogenesis of ascites in cirrhotics as well. It has been hypothesized that the progression from ascites to hepatorenal syndrome is a spectrum where splanchnic vasodilation defines both resistance to diuretic medications in ascites (which is commonly seen in type 2 HRS) and the onset of kidney vasoconstriction (as described above) leading to hepatorenal syndrome. Prevention
The risk of death in hepatorenal syndrome is very high; consequently, there is a significant emphasis on the identification of patients who are at risk for HRS, and prevention of triggers for onset of HRS. As infection (specifically spontaneous bacterial peritonitis) and gastrointestinal hemorrhage are both complications in individuals with cirrhosis, and are common triggers for HRS, specific care is made in early identification and treatment of cirrhotics with these complications  to prevent HRS. Some of the triggers for HRS are induced by treatment of ascites and can be preventable. The aggressive use of diuretic medications should be avoided. In addition, many medications that are either used to treat cirrhotic complications (such as some antibiotics) or other conditions may cause sufficient impairment in kidney function in the cirrhotic to lead to HRS.