vasoconstriction (as described above) leading to hepatorenal syndrome. prevention picture of the esophagus at the time of endoscopy showing prominent esophageal varices. bleeding from esophageal varices can be a precipitant for hepatorenal syndrome in individuals with cirrhosis, and can be prevented by early diagnosis and treatment. 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. also, large volume paracentesis—which is the removal of ascites fluid from the abdomen using a needle or catheter in order to relieve discomfort—may cause enough alteration in hemodynamics to precipitate hrs, and should be avoided in individuals at risk. the concomitant infusion of albumin can avert the circulatory dysfunction that occurs after large-volume paracentesis and may prevent hrs. conversely, in individuals with very tense ascites, it has been hypothesized that removal of ascitic fluid may improve kidney function if it decreases the pressure on the renal veins. individuals with ascites that have become infected spontaneously (termed spontaneous bacterial peritonitis or sbp) are at an especially high risk for the development of hrs. in individuals with sbp, one randomized controlled trial found that the administration of intravenous albumin on the day of admission and on the third day in hospital reduced both the rate of kidney insufficiency and the mortality rate. treatment transplantation the definitive treatment for hepatorenal syndrome is liver transplantation, and all other therapies can best be described as bridges to transplantation. while liver transplantation is by far the best available management option for hrs, the mortality of individuals with hrs has been shown to be as high as 25% within the first month after transplantation. individuals with hrs and evidence of greater hepatic dysfunction (quantified as meld scores above 36) have been found to be at greatest risk of early mortality after liver transplantation. a further deterioration of kidney function even after liver transplantation in individuals with hrs has been demonstrated in several studies; however, this is transient and thought to be due to the use of medications with toxicity to the kidneys, and specifically the introduction of immunosuppressants such as tacrolimus and cyclosporine that are known to worsen kidney function. over the long-term, however, individuals with hrs who are the recipients of liver transplants almost universally recover kidney function, and studies show that their survival rates at three years are similar to those who have received liver transplants for reasons other than hrs. in anticipation of liver transplantation (which may be associated with considerable in-hospital delay), several other strategies have been found to be beneficial in preserving kidney function. these include the use of intravenous albumin infusion, medications (for which the best evidence is for analogues of vasopressin, which causes splanchnic vasoconstriction), radiological shunts to decrease pressure in the portal vein, dialysis, and a specialized albumin-bound membrane dialysis system termed molecular adsorbents recirculation system (mars) or liver dialysis. medical therapy many major studies showing improvement in kidney function in patients with hepatorenal syndrome have involved expansion of the volume of the plasma with albumin given intravenously. the quantity of albumin administered intravenously varies: one cited regimen is 1 gram of albumin per kilogram of body weight intravenously on the first day, followed by 20 to 40 grams daily. notably, studies have shown that treatment with albumin alone is inferior to treatment with other medications in conjunction with albumin; most studies evaluating pre-transplant therapies for hrs involve the use of albumin in conjunction with other medical or procedural treatment. midodrine is an alpha-agonist and octreotide is an analogue of somatostatin, a hormone involved in regulation of blood vessel tone in the gastrointestinal tract. the medications are respectively systemic vasoconstrictors and inhibitors of splanchnic vasodilation, and were not found to be useful when used individually in treatment of hepatorenal syndrome. however, one study of 13 patients with hepatorenal syndrome showed significant improvement in kidney function when the two were used together (with midodrine given orally, octreotide given subcutaneously and both dosed according to blood pressure), with three patients surviving to discharge. another nonrandomized, observational study of individuals with hrs treated with subcutaneous octreotide and oral midodrine showed that there was increased survival at 30 days. the vasopressin analogue ornipressin was found in a number of studies to be useful in improvement of kidney function in patients with hepatorenal syndrome, but has been limited in its use, as it can cause severe ischemia to major organs. terlipressin is a vasopressin analogue that has been found in one large study to be useful for improving kidney function in patients with hepatorenal syndrome with a lesser incidence of ischemia but is not available in the united states. a randomized control trial led by florence wong demonstrated improved renal function in individuals with type 1 hrs treated with terlipressin and albumin over placebo. a key criticism of all of these medical therapies has been heterogeneity in the populations investigated and the use of kidney function, instead of mortality, as an outcome measure. other agents that have been investigated for use in treatment of hrs include pentoxifylline, acetylcysteine, and misoprostol. the evidence for all of these therapies is based on either case series, or in the case of pentoxifylline, extrapolated from a subset of patients treated for alcoholic hepatitis. procedural treatments tips, shown in progress here, has been shown to improve kidney function in individuals with hrs if portal pressures decrease after the procedure. a transjugular intrahepatic portosystemic shunt (tips) involves the decompression of the high pressures in the portal circulation by placing a small stent between a portal and hepatic vein. this is done through radiologically guided catheters which are passed into the hepatic vein either through the internal jugular vein or the femoral vein. theoretically, a decrease in portal pressures is thought to reverse the hemodynamic phenomena that ultimately lead to the development of hepatorenal syndrome. tips has been shown to improve kidney function in patients with hepatorenal syndrome. complications of tips for treatment of hrs include the worsening of hepatic encephalopathy (as the procedure involves the forced creation of a porto-systemic shunt, effectively bypassing the ability of the liver to clear toxins), inability to achieve adequate reduction in portal pressure, and bleeding. liver dialysis involves extracorporeal dialysis to remove toxins from the circulation, usually through the addition of a second dialysis circuit that contains an albumin-bound membrane. the molecular adsorbents recirculation system (mars) has shown some utility as a bridge to transplantation in patients with hepatorenal syndrome, yet the technique is still nascent. renal replacement therapy may be required to bridge individuals with hepatorenal syndrome to liver transplantation, although the condition of the patient may dictate the modality used. the use of dialysis, however, does not lead to recuperation or preservation of kidney function in patients with hrs, and is essentially only used to avoid complications of kidney failure until transplantation can take place. in patients who undergo hemodialysis, there may even be an increased risk of mortality due to low blood pressure in patients with hrs, although appropriate studies have yet to be performed. as a result, the role of renal replacement therapy in patients with hrs remains unclear. epidemiology as the majority of individuals with hepatorenal syndrome have cirrhosis, much of the epidemiological data on hrs comes from the cirrhotic population. the condition is quite common: approximately 10% of individuals admitted to hospital with ascites have hrs. a retrospective case series of cirrhotic patients treated with terlipressin suggested that 20.0% of acute kidney failure in cirrhotics was due to type 1 hrs, and 6.6% was due to type 2 hrs. it is estimated that 18% of individuals with cirrhosis and ascites will develop hrs within one year of their diagnosis with cirrhosis, and 39% of these individuals will develop hrs within five years of diagnosis. 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 first systematic attempt to define hepatorenal syndrome was made in 1994 by the international ascites club, a group of liver specialists. the more recent history of hrs has involved elucidation of the various vasoactive mediators that cause the splanchnic and kidney blood flow abnormalities of the condition.