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INTRODUCTION — The hepatorenal syndrome is one of many potential causes of acute kidney injury in patients with acute or chronic liver disease. Affected patients usually have portal hypertension due to cirrhosis, severe alcoholic hepatitis, or (less often) metastatic tumors, but can also have fulminant hepatic failure from any cause [1-3]. The hepatorenal syndrome represents the end-stage of a sequence of reductions in renal perfusion induced by increasingly severe hepatic injury. The hepatorenal syndrome is a diagnosis of exclusion and is associated with a poor prognosis.
This topic will review the hepatorenal syndrome in detail. Overviews of the complications of fulminant hepatic failure and cirrhosis are provided elsewhere. (See "Acute liver failure in adults: Management and prognosis" and "Cirrhosis in adults: Overview of complications, general management, and prognosis".)
PATHOGENESIS — Arterial vasodilatation in the splanchnic circulation, which is triggered by portal hypertension, appears to play a central role in the hemodynamic changes and the decline in renal function in cirrhosis [1-3]. The presumed mechanism is increased production or activity of vasodilators, mainly in the splanchnic circulation, with nitric oxide thought to be most important [1,4,5].
As the hepatic disease becomes more severe, there is a progressive rise in cardiac output and fall in systemic vascular resistance; the latter change occurs despite local increases in renal and femoral vascular resistance that result in part from hypotension-induced activation of the renin-angiotensin and sympathetic nervous systems (figure 1) [1-3,6]. Thus, the reduction in total vascular resistance results from decreased vascular resistance in the splanchnic circulation , perhaps in part under the influence of nitric oxide derived from the endothelium. Bacterial translocation from the intestine into the mesenteric lymph nodes may play an important role in this process [1,7,8]. A review of the hemodynamic changes seen with progressive cirrhosis can be found in a separate topic review. (See "Pathogenesis of ascites in patients with cirrhosis".)
The decline in renal perfusion in this setting is associated with reductions in glomerular filtration rate (GFR) and sodium excretion (often to less than 10 meq/day in advanced cirrhosis) [9,10] and a fall in mean arterial pressure, despite the intense renal vasoconstriction . The importance of splanchnic vasodilatation in these changes can be indirectly illustrated by the response to ornipressin, an analog of antidiuretic hormone (arginine vasopressin) that is a preferential splanchnic vasoconstrictor .
In patients with advanced cirrhosis, the administration of ornipressin or other vasopressin analogues partially corrects many of the systemic and renal hemodynamic abnormalities that are present (figure 2); these include an elevation in mean arterial pressure, reductions in plasma renin activity and norepinephrine concentration, and increases in renal blood flow, GFR (from 18 to 29 mL/min), and urinary sodium excretion and volume.
In addition, acutely lowering renal sympathetic tone and renal vascular resistance in the early stages of hepatorenal syndrome by the intravenous administration of the sympatholytic agent, clonidine, can raise the GFR by as much as 25 percent . However, this benefit does not appear to be sustained with chronic oral therapy, despite a persistent reduction in sympathetic activity .
The response to creation of a portasystemic shunt also supports the importance of splanchnic hemodynamics in the genesis of the hepatorenal syndrome. Portasystemic shunting has improved renal function in a limited number of patients with the hepatorenal syndrome , but it is infrequently used as treatment for this disorder . One report, however, suggested that the reduction in intrahepatic pressure induced by this modality may prevent the development of the hepatorenal syndrome. This retrospective study evaluated 204 patients with variceal bleeding who were treated with either a portasystemic shunt or sclerotherapy (or other non-shunt modalities) . Portasystemic shunting was associated with a lower incidence of ascites (15 versus 73 percent) and hepatorenal syndrome (4 versus 21 percent), a higher incidence of encephalopathy, and no difference in overall patient survival.
EPIDEMIOLOGY — Patients who develop the hepatorenal syndrome usually have portal hypertension due to cirrhosis, severe alcoholic hepatitis, or, less often, metastatic tumors [1-3]. However, patients with fulminant hepatic failure from any cause may develop hepatorenal syndrome.
The incidence of hepatorenal syndrome was evaluated in a prospective study of 229 nonazotemic patients with cirrhosis and ascites: the hepatorenal syndrome developed in 18 and 39 percent at one and five years, respectively . Patients with hyponatremia and a high plasma renin activity were at highest risk. These signs of neurohumoral activation presumably reflected a more severe decline in effective perfusion [1,6].
Hepatorenal syndrome also occurs frequently in patients with acute liver disease. In a study of patients with alcoholic hepatitis, for example, hepatorenal syndrome occurred in 28 of 101 patients .
Although hepatorenal syndrome can be seen in most forms of severe hepatic disease, patients with primary biliary cirrhosis appear relatively protected . Sodium retention, ascites formation, and the hepatorenal syndrome all tend to occur less often in primary biliary cirrhosis, possibly due in part to the natriuretic and renal vasodilator actions of retained bile salts.
CLINICAL PRESENTATION — The hepatorenal syndrome is characterized by the following features in a patient who has established or clinically evident acute or chronic liver disease [1-3,10,19]:
However, not all patients with hepatorenal syndrome have oliguria (especially early in its course), a progressive rise in serum creatinine, and a benign urine sediment. Urine volumes may be higher than previously appreciated. Some studies, for example, have found that the urine volume may exceed 400 mL per day, with markedly lower output being observed only within a few days from death [20,21]. In addition, the serum creatinine may increase by as little as 0.1 mg/dL (9 micromol/L) per day, with intermittent periods of stabilization or even slight improvement. Lastly, the urine sediment may show a variety of abnormalities, such as hematuria due to bladder instrumentation and underlying coagulopathy, and granular casts due to hyperbilirubinemia.
Based upon the rapidity of the decline in kidney function, two forms of hepatorenal syndrome have been described [1,19,22]:
Precipitants — The onset of renal failure is typically insidious but can be precipitated by an acute insult, such as bacterial infection or gastrointestinal bleeding [10,19,23]. Spontaneous bacterial peritonitis, for example, can trigger progressive hepatorenal syndrome, although it is more likely to occur in patients who already have some degree of renal insufficiency [24,25]. (See "Spontaneous bacterial peritonitis in adults: Treatment and prophylaxis", section on 'Renal dysfunction'.)
Although overly rapid diuresis has often been mentioned as a precipitant of hepatorenal syndrome, perhaps because most patients are taking diuretics when the syndrome is diagnosed, diuretics do not cause hepatorenal syndrome. Diuretics can, however, cause azotemia, particularly if fluid is removed too rapidly in patients without peripheral edema. Diuretic-induced azotemia improves with the cessation of therapy and fluid repletion. In comparison, the hepatorenal syndrome typically worsens inexorably, even after diuretics are stopped. (See "Ascites in adults with cirrhosis: Initial therapy", section on 'Diuretic therapy'.)
Problems with estimating kidney function — Patients with hepatorenal syndrome may have renal dysfunction that is substantially more severe than is suggested by the serum creatinine. Both urea and creatinine production may be substantially reduced in this setting, due to the liver disease and to decreased muscle mass and decreased protein and meat intake. The net effect is that a serum creatinine that appears to be within the normal range (eg, 1 to 1.3 mg/dL [88.4 to 115 micromol/L]) may be associated with a glomerular filtration rate (GFR) that ranges from as low as 20 to 60 mL/min to a clearly normal value above 100 mL/min, depending primarily upon muscle mass. (See "Assessment of kidney function", section on 'Using creatinine to estimate GFR'.)
The blood urea nitrogen (BUN) is variable in these patients. For a given GFR, it may be lower or higher than expected. If protein intake is very low, reduced urea production may result in a low BUN and a low BUN to creatinine ratio. In contrast, if protein intake is adequate, increased passive reabsorption of urea in the proximal tubule, driven by enhanced proximal tubular reabsorption of sodium and water, can result in a high BUN and a high BUN to creatinine ratio. (See "Etiology and diagnosis of prerenal disease and acute tubular necrosis in acute kidney injury (acute renal failure)".)
DIAGNOSIS — Hepatorenal syndrome is diagnosed based upon clinical criteria. There is no one specific test that can establish the diagnosis. Investigational urinary biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) tend to be lower in prerenal azotemia and hepatorenal syndrome than in acute tubular necrosis (ATN), but there is considerable overlap between these conditions [26,27]. In addition, hepatorenal syndrome is a diagnosis of exclusion, meaning that other potential etiologies of acute or subacute kidney injury in patients with liver disease should be considered unlikely before a diagnosis of hepatorenal syndrome is made.
The following definition and diagnostic criteria have been proposed for the hepatorenal syndrome [1,19,22]:
As noted above, patients diagnosed with hepatorenal syndrome are classified as type 1 hepatorenal syndrome (more severe) or type 2 hepatorenal syndrome (less severe) based upon the rapidity of the acute kidney injury and the degree of renal impairment. Type 1 hepatorenal syndrome is present if the serum creatinine increases by at least twofold to a value greater than 2.5 mg/dL (221 micromol/L) during a period of less than two weeks. Less rapidly progressive disease is classified as type 2.
DIFFERENTIAL DIAGNOSIS — The diagnosis of the hepatorenal syndrome is one of exclusion, entertained only after other potential causes of acute or subacute kidney injury have been ruled out . As examples:
Obesity with fatty liver is a relatively common cause of cirrhosis. Many of these patients have diabetes and can develop diabetic nephropathy. (See "Epidemiology, clinical features, and diagnosis of nonalcoholic fatty liver disease in adults".) A prospective study from 2011 that analyzed 562 patients with cirrhosis and renal function impairment at a single center found that hepatorenal syndrome was less common than prerenal or infection-associated kidney injury . Of the 463 patients in this study in whom a diagnosis could be made, the following frequencies were noted:
The frequency of acute tubular necrosis (ATN) in this study was not defined, although older case series report that 10 to 20 percent of patients with acute kidney injury in the setting of cirrhosis have ATN . It is possible that ATN is less common now, due to avoidance of nephrotoxins such as nonsteroidal anti-inflammatory drugs and aminoglycosides in these patients. In addition, some experts believe that some patients with ongoing infection (principally spontaneous bacterial peritonitis in the absence of septic shock) can have hepatorenal syndrome since a substantial proportion of such patients (18 percent in one report) have persistent or progressive kidney injury despite successful antibiotic therapy for peritonitis . Thus, as mentioned above, the presence of spontaneous bacterial peritonitis should not exclude the diagnosis of hepatorenal syndrome.
Kidney biopsy is not commonly performed in patients with cirrhosis and acute kidney injury, particularly when there is minimal hematuria and proteinuria. As an example, in a series of 65 patients with cirrhosis and renal disease who underwent transjugular kidney biopsy, only 18 patients had no proteinuria and no hematuria . Of these 18 patients, glomerular lesions were identified in ten (such as IgA nephropathy, membranoproliferative glomerulonephritis, or diabetic nephropathy), and ATN was identified in seven. Transjugular kidney biopsy, performed by an interventional radiologist, can be considered if the result may have an impact on treatment and if such treatment could outweigh the potential harms associated with the interventional procedure. Although there is a common misconception that the kidneys are histologically normal, a relatively specific but subtle and reversible renal lesion has been described—glomerular tubular reflux .
Distinguishing the hepatorenal syndrome from these other disorders is clinically important because of the marked difference in prognosis. ATN and most causes of prerenal disease are generally reversible. In contrast, the prognosis is poor in the hepatorenal syndrome (especially type 1), with most patients dying within weeks of the onset of renal injury unless liver transplantation is performed or effective treatment is given [10,32].
Acute tubular necrosis — Patients with cirrhosis may develop ATN after a course of aminoglycoside therapy, the administration of a radiocontrast agent, or an episode of sepsis or bleeding with a decrease in blood pressure . The presence of ATN is usually suspected from the history and from the often rapid rise in the serum creatinine, which contrasts to the usually gradual rise in hepatorenal syndrome. An unresolved issue is whether the prolonged renal ischemia in the hepatorenal syndrome can, in some cases, lead to ATN [1,19].
Some of the traditional laboratory methods used to distinguish prerenal disease from ATN may not be helpful in patients with hepatic disease. As an example, ATN is usually associated with a fractional excretion of sodium above 2 percent and granular and epithelial cell casts in the urine sediment. Calculators are available to compute the fractional excretion of sodium: (calculator 1) and (calculator 2).
However, the fractional excretion of sodium may remain below 1 percent in patients with cirrhosis who develop ATN due to the persistent renal ischemia induced by the hepatic disease . The urinalysis also may be misleading. Granular and epithelial cell casts may be seen with marked hyperbilirubinemia alone and are therefore not diagnostic of ATN; how this occurs is not understood. (See "Etiology and diagnosis of prerenal disease and acute tubular necrosis in acute kidney injury (acute renal failure)" and "Fractional excretion of sodium, urea, and other molecules in acute kidney injury (acute renal failure)".)
Prerenal disease — The hepatorenal syndrome has been difficult to distinguish from prerenal azotemia. Prerenal disease in patients with cirrhosis can be induced by gastrointestinal fluid losses, bleeding, or therapy with a diuretic or a nonsteroidal anti-inflammatory drug (since renal vasodilator prostaglandins in part maintain renal perfusion in this setting) [1,34]. (See "NSAIDs: Acute kidney injury (acute renal failure)".)
Thus, the diagnosis of the hepatorenal syndrome requires that there be no improvement in renal function following discontinuation of potential nephrotoxins and a trial of fluid repletion. In addition, emerging kidney biomarkers may prove helpful in distinguishing prerenal disease, hepatorenal syndrome, and ATN in patients with cirrhosis .
Approach to therapy — The ideal therapy for hepatorenal syndrome is improvement of liver function from recovery of alcoholic hepatitis, treatment of decompensated hepatitis B with effective antiviral therapy, recovery from acute hepatic failure, or liver transplantation [35,36]. The ability of liver function to improve with abstinence from alcohol and effective antiviral therapy of hepatitis B is remarkable. (See 'Improving hepatic function' below.)
However, when improvement of liver function is not possible in the short term, we recommend that medical therapy be instituted in an attempt to reverse the acute kidney injury associated with hepatorenal syndrome. Our suggestions regarding the choice of medical therapy depend upon several factors, including: whether the patient is admitted to the intensive care unit; the availability of certain drugs, for which there is national and regional variability; and whether the patient is a candidate for liver transplantation:
The goal of medical therapy or TIPS in patients with hepatorenal syndrome is reversal of the acute kidney injury. In addition, when patients are treated with norepinephrine, terlipressin, or midodrine plus octreotide, an immediate goal of therapy is to raise the mean arterial pressure by approximately 10 to 15 mmHg. In a systematic review of 501 patients with hepatorenal syndrome from 21 studies, the magnitude of the increase in mean arterial pressure induced by these vasoconstrictors was significantly associated with the magnitude of the decrease in serum creatinine . As an example, a 9 mmHg increase in mean arterial pressure predicted a 1 mg/dL (88.4 micromol/L) decrease in serum creatinine. The authors also predicted that an increase in mean arterial pressure of 9 to 13 mmHg would be necessary to achieve resolution in most patients with type 1 hepatorenal syndrome.
In patients treated with norepinephrine, terlipressin, or octreotide, we usually treat for a total of two weeks. However, we and others occasionally treat for longer durations (up to one month or more) if there is some but not complete improvement in renal function after two weeks of therapy. In patients who respond to therapy, we occasionally treat indefinitely with midodrine to maintain a higher mean arterial pressure (or until liver transplantation or resolution of liver injury). Many patients who recover from type 1 hepatorenal syndrome continue to have refractory ascites, and midodrine may be effective in such patients . In contrast, if a patient has no improvement in renal function after two weeks, therapy with these drugs can be considered futile.
The following sections will review the different therapies that have been evaluated in the treatment of hepatorenal syndrome. Issues related to the treatment of ascites in patients with cirrhosis (eg, fluid and sodium intake, diuretic therapy) are discussed separately. (See "Ascites in adults with cirrhosis: Initial therapy" and "Ascites in adults with cirrhosis: Diuretic-resistant ascites" and 'Precipitants' above.)
Improving hepatic function — The best hope for reversal of the renal failure is an improvement in hepatic function due to partial resolution of the primary disease or to successful liver transplantation [39-41]. Improvement in the underlying liver disease is most impressive in patients with alcoholic liver disease (particularly severe alcoholic hepatitis) with abstinence or with decompensated cirrhosis due to hepatitis B virus infection treated with lamivudine [42,43].
Norepinephrine for patients in the intensive care unit — Although not usually available on the general medical ward, norepinephrine can be administered in the intensive care unit and has been used successfully in patients with hepatorenal syndrome . Vasopressin, also available in the intensive care unit, may be effective in patients with hepatorenal syndrome .
In an open-label trial, 46 patients with type 1 hepatorenal syndrome (mean serum creatinine, 3.2 mg/dL [283 micromol/L]) were randomly assigned to receive combination therapy with terlipressin plus albumin or norepinephrine plus albumin (using the doses described above) . Treatment was administered for 15 days, and all patients were followed for a month. The following results were obtained, neither of which were statistically significant:
Although the efficacy and safety of terlipressin and norepinephrine appeared similar, the cost of terlipressin therapy was more than three times the cost of norepinephrine therapy . A second, smaller trial reached a similar conclusion : after 14 days of therapy, reversal of hepatorenal syndrome occurred in ten of twelve patients treated with terlipressin and seven of ten patients treated with norepinephrine; the adverse event rate was also similar between the groups; and the cost of therapy was 14 times greater with terlipressin.
Thus, we suggest norepinephrine rather than terlipressin or other therapies for treatment of hepatorenal syndrome who are admitted to the intensive care unit.
Patients not in the intensive care unit — Optimal medical therapy for patients with hepatorenal syndrome who are not admitted to the intensive care unit varies according to whether terlipressin is available.
Terlipressin plus albumin where available — Vasopressin and its analogs (ornipressin and terlipressin) should theoretically reduce splanchnic vasodilation. As an example, when ornipressin was administered in combination with either infusion of albumin or a peritoneovenous shunt (to expand the effective arterial blood volume and reduce the release of vasoconstrictors such as angiotensin II and norepinephrine), there was an increase in glomerular filtration rate (GFR) (figure 2) [11,48,49]. However, this regimen may also induce significant renal ischemia .
Another vasopressin analog, terlipressin, has also been examined as a treatment for hepatorenal syndrome in several randomized trials [50-55]. A 2012 Cochrane meta-analysis synthesized the results from these trials ; of the six trials included, three compared terlipressin plus albumin with albumin alone, one compared terlipressin alone with albumin alone, and two compared terlipressin alone with either placebo or no therapy. Only one of the trials was double blind; the dose and duration of terlipressin therapy varied across studies. The following findings were reported:
These data suggest that terlipressin therapy may improve renal function and reduce mortality. Thus, for patients with hepatorenal syndrome who are not admitted to the intensive care unit, we suggest combination therapy with terlipressin plus albumin rather than other therapies. However, terlipressin is not available in the United States. When terlipressin is not available, combination therapy with midodrine, octreotide, and albumin is used for patients not in the intensive care unit. (See 'Midodrine, octreotide, and albumin where terlipressin is not available' below.)
Midodrine, octreotide, and albumin where terlipressin is not available — Therapy with midodrine (a selective alpha-1 adrenergic agonist), octreotide (a somatostatin analog), and albumin may be highly effective and safe in patients with hepatorenal syndrome. Midodrine is a systemic vasoconstrictor, and octreotide is an inhibitor of endogenous vasodilator release (which produces splanchnic vasoconstriction); combined therapy theoretically improves renal and systemic hemodynamics .
In a nonrandomized study of 13 consecutive patients with type 1 hepatorenal syndrome, the first eight were treated with intravenous dopamine (2 to 4 mcg/kg per min) and the last five patients were treated with oral midodrine (7.5 to 12.5 mg three times daily) plus octreotide (100 to 200 mcg subcutaneously three times daily) . Both groups also received intravenous albumin daily during treatment. The goal of therapy was to raise the mean arterial pressure by 15 mmHg. The following results were reported:
Additional data substantiate the potential efficacy and safety of octreotide and midodrine. In a retrospective study, 60 patients with hepatorenal syndrome were treated with midodrine (up to 15 mg three times daily), octreotide (200 mcg subcutaneously three times daily), and albumin, and 21 concurrent patients only received albumin . Therapy with midodrine and octreotide was associated with significantly lower mortality (43 versus 71 percent) and a significantly higher proportion of patients who had resolution of hepatorenal syndrome (40 versus 10 percent).
In our experience, the speed with which effective treatment is achieved appears to be important. Thus, we prefer continuous infusion of octreotide at 50 mcg/hr rather than subcutaneous injection. This can be delivered on a general medical ward. The midodrine dose should be increased with each consecutive dose in order to achieve an increase in blood pressure rapidly. It is our experience that 15 mg three times per day may be more effective than 12.5 mg three times per day. Changing the dose after 24 hours on the prior dose raises the blood pressure too slowly and may lead to failure of therapy.
In contrast to combination therapy with midodrine and octreotide, octreotide monotherapy does not appear to be beneficial. In a randomized crossover study, 14 patients with hepatorenal syndrome were treated with four days of octreotide plus albumin and four days of albumin alone in random order . Response to therapy was identical with both treatments. Midodrine alone or in combination with albumin (but without octreotide) has not been evaluated in patients with type 1 hepatorenal syndrome.
Thus, for patients with hepatorenal syndrome who are not admitted to the intensive care unit and for whom terlipressin is unavailable, we suggest combination therapy with octreotide, midodrine, and albumin rather than other therapies.
Patients who do not respond to initial medical therapy — Treatment options for patients who do not respond to one of the medical therapies listed above include TIPS and dialysis.
Transjugular intrahepatic portosystemic shunt — The transjugular intrahepatic portosystemic shunt (TIPS) has been used in the treatment of refractory ascites. (See "Transjugular intrahepatic portosystemic shunts: Indications and contraindications".)
When used in this setting, there may also be a delayed improvement in renal function [60-64]. In one study, for example, the average plasma creatinine concentration was 1.5 mg/dL (132 micromol/L) at baseline, was unchanged at one week, and fell to 0.9 mg/dL (80 micromol/L) by six months . In another series, there was a nonsignificant trend toward an increase in GFR (65 mL/min at baseline to 76 mL/min at four weeks) .
There is much less information on the use of TIPS in patients who fulfill criteria for the hepatorenal syndrome . One report described 16 such patients, six of whom had severe hepatorenal syndrome (defined as a serum creatinine of 2.5 mg/dL [220 micromol/L] or higher, or a creatinine clearance below 20 mL/min) . Within two weeks, there was an approximate doubling of the creatinine clearance with a proportionate reduction in the serum creatinine and an increase in urinary sodium excretion. Additional improvements in renal function occurred over the ensuing six to eight weeks. Only three patients failed to respond, all of whom died within six weeks after TIPS.
Another series evaluated seven patients with cirrhosis and hepatorenal syndrome, defined as a doubling of the serum creatinine to more than 2.5 mg/dL (221 micromol/L) or a 50 percent reduction in creatinine clearance to below 20 mL/min in less than two weeks, despite volume expansion . Insertion of a TIPS was associated with a gradual improvement in GFR (9 to 27 mL/min), reductions in the blood urea nitrogen (BUN) and serum creatinine, and, in most patients, a reduction in the activity of the renin-angiotensin and sympathetic nervous systems suggesting an improvement in systemic hemodynamics. The average survival following TIPS placement was approximately five months, which is longer than the expected survival of such patients.
Unfortunately, many patients with hepatorenal syndrome are too ill to undergo TIPS. In a study that devised a prediction model to determine survival following elective TIPS, those patients with type 1 hepatorenal syndrome have a predicted 90 day mortality following TIPS of at least 25 percent if cirrhosis is due to alcoholic or cholestatic liver disease and at least 80 percent if cirrhosis is due to other causes . A prediction model scoring system based upon the survival of 231 patients who underwent elective TIPS was devised to predict survival after the procedure.
In addition, TIPS is associated with various complications :
Overall, these results suggest that, in selected patients with hepatorenal syndrome, TIPS may provide short-term benefit. Given the risks associated with this procedure (particularly the high incidence of encephalopathy), it should be considered only as a last resort in selected patients.
Dialysis — Patients with hepatorenal syndrome who progress to renal failure can be treated with dialysis, which is most commonly done when patients are awaiting a liver transplant or when there is the possibility of improvement in liver function. In addition, dialysis improves the priority score for the transplant in the United States. In one retrospective, single-center study, 30 percent of patients who required dialysis survived to liver transplantation .
Survival on dialysis is generally limited by the severity of the hepatic failure , as well as concurrent respiratory failure . Patients with an acute and potentially reversible hepatic insult may particularly benefit from dialysis since renal function will recover in parallel with improving hepatic function .
Hemodialysis is frequently difficult to perform in patients with hepatorenal syndrome since decompensated hepatic function is associated with hemodynamic instability. Some success has been realized with continuous renal replacement modalities . (See "Continuous renal replacement therapy in acute kidney injury (acute renal failure)".)
Other therapies — A number of other drugs have been tried for the treatment of hepatorenal syndrome, such as misoprostol, N-acetylcysteine, and angiotensin-converting enzyme inhibitors. None of these approaches are consistently associated with benefit, and therefore none are recommended. In rare patients, a peritoneovenous shunt is used.
Peritoneovenous shunt — A peritoneovenous shunt, which drains peritoneal fluid from the peritoneum into the internal jugular vein, reinfuses ascites into the vascular space. This modality has been used in patients with refractory ascites and renal failure due to the hepatorenal syndrome [32,70-74]. In these settings, the increase in fluid return to the cardiopulmonary circulation can lead sequentially to decreased activity of sodium-retaining and vasoconstrictive mechanisms (such as the renin-angiotensin-aldosterone system), a marked rise in urinary sodium excretion, and a modest elevation in GFR [32,70,73].
However, it is now rarely used because of an appreciable rate of complications and the lack of evidence that peritoneovenous shunting prolongs patient survival, which may be several years in patients with normal or near-normal hepatic and renal function tests but less than six weeks in patients with the hepatorenal syndrome [32,71,72,75,76].
The major problem with the peritoneovenous shunt is the relatively high rate of complications, including disseminated intravascular coagulation (due to entry into the blood stream of endotoxin or other procoagulant material in the ascitic fluid), infection of the shunt, which can lead to bacteremia, variceal bleeding resulting from volume expansion and a concurrent rise in portal venous pressure, and small bowel obstruction [70,77,78].
The net effect is that the perioperative mortality can reach 25 percent in patients with advanced disease [77,78]. In comparison, peritoneovenous shunting is relatively well-tolerated in patients with ascites but relatively normal renal function [71,72]. Furthermore, the perioperative morbidity can be diminished if, prior to insertion of the shunt, there is intraoperative drainage of the ascites, which is then replaced by 5 liters of isotonic saline [71,78]. This regimen can minimize those complications related to massive ascites infusion: disseminated intravascular coagulation and increased portal pressure.
The only remaining indications for peritoneovenous shunt are:
PREVENTION — Hepatorenal syndrome regularly develops in patients with systemic bacterial infection (eg, spontaneous bacterial peritonitis [SBP]) and/or severe alcoholic hepatitis. The following therapies may prevent the development of hepatorenal syndrome in these patients:
PROGNOSIS — Overall, the mortality of patients with liver failure is substantially worse if they develop hepatorenal syndrome . Without therapy, most patients die within weeks of the onset of the renal impairment. In turn, the outcome of patients with hepatorenal syndrome, as well as recovery of kidney function, is strongly dependent upon reversal of the hepatic failure, whether spontaneous, following medical therapy, or following successful liver transplantation .
The rate of recovery of kidney function following recovery of liver failure is uncertain; reported rates are affected by varying pretransplant kidney function and differences over time in indications for dialysis and in eligibility for liver transplantation. However, a substantial proportion of patients who have progressed to dialysis and survive to receive a liver transplant do recover kidney function . (See "Renal function and nonrenal solid organ transplantation".)
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