Hepatorenal syndrome: Treatment and prognosis

INTRODUCTION — 

Hepatorenal syndrome-acute kidney injury (HRS-AKI) is an acute, severe form of cirrhosis-mediated kidney dysfunction. Patients with HRS-AKI usually are ill with liver failure, manifesting as jaundice and coagulopathy, and often have other complications of cirrhosis such as variceal bleeding or hepatic encephalopathy. In addition, such patients also may have circulatory or respiratory failure. Less commonly, patients with decompensated cirrhosis and ascites may have HRS-AKI without dysfunction in other organs or organ systems; this is most likely in those whose underlying liver disease has been treated (eg, cured hepatitis C or long-term abstinence from alcohol).

This topic will review the treatment and prognosis of HRS-AKI. The clinical presentation and diagnosis of HRS-AKI, as well as overviews of the complications of fulminant hepatic failure and cirrhosis, are presented elsewhere:

●(See "Hepatorenal syndrome: Clinical presentation and diagnosis".)

●(See "Acute liver failure in adults: Management and prognosis".)

●(See "Cirrhosis in adults: Overview of complications, general management, and prognosis".)

GENERAL MEASURES IN ALL PATIENTS — 

In addition to the general measures applicable to all patients with acute kidney injury (AKI), such as avoidance of hypotension and nephrotoxins (see "Overview of the management of acute kidney injury (AKI) in adults"), general measures for patients with hepatorenal syndrome-AKI (HRS-AKI) include a search for and treatment of HRS-AKI precipitants such as infection, gastrointestinal bleeding, or volume depletion from aggressive diuresis or overzealous lactulose administration. (See "Hepatorenal syndrome: Clinical presentation and diagnosis", section on 'Precipitants'.)

General measures for patients with HRS-AKI are as follows [1,2]:

Prompt treatment of infection — We promptly evaluate and treat potential sources of infection. If the suspicion for infection (eg, spontaneous bacterial peritonitis) is high, we administer empiric antibiotics. Antibiotics are discontinued if the infectious disease evaluation is negative. (See "Hepatorenal syndrome: Clinical presentation and diagnosis", section on 'Diagnostic evaluation'.)

Avoidance of volume depletion — Maintaining adequate intravascular volume is essential to the successful treatment of HRS-AKI. This is accomplished by the following:

●Prompt, appropriate transfusion of red blood cells in the setting of blood loss. (See "Overview of the management of patients with variceal bleeding".)

●Cessation of diuretic therapy.

●Adjustment of lactulose dose to minimize diarrhea.  

We generally avoid large-volume paracentesis, even with colloid replacement, in patients with HRS-AKI to prevent postprocedure volume shifts out of the central circulation. However, practice patterns vary in this setting.  

Beta-blocker cessation — We typically stop beta-blocker therapy in patients with HRS-AKI. Many patients with cirrhosis are treated with nonselective beta-blockers (eg, nadolol or carvedilol) to prevent bleeding from esophageal varices. However, these medications may contribute to kidney dysfunction in patients with HRS-AKI by decreasing blood pressure or interfering with vasoconstrictor therapy [3]. (See 'Medical therapy' below.)

Upper endoscopy should be performed in patients taking beta-blockers who are known to have large varices. Variceal banding may be necessary to prevent bleeding after beta-blocker withdrawal [4].

MEDICAL THERAPY — 

The definitive treatment for hepatorenal syndrome-acute kidney injury (HRS-AKI) is a liver transplant, not medical therapy. Vasoconstrictors and adjunctive intravenous (IV) albumin are best used as a bridge to liver transplantation.

Vasoconstrictors — Vasoconstrictors are the mainstay of medical treatment for HRS-AKI. They address the underlying pathophysiology of HRS-AKI by inducing splanchnic vasoconstriction, which ultimately improves kidney perfusion. (See "Hepatorenal syndrome: Clinical presentation and diagnosis", section on 'Pathogenesis'.)

Terlipressin preferred

●Terlipressin as first-line therapy – Terlipressin is the preferred vasoconstrictor for the treatment of HRS-AKI [4-8]. The main reason to use alternative vasoconstrictor therapies such as norepinephrine or midodrine plus octreotide is unavailability of terlipressin. Most patients with HRS-AKI who have absolute or relative contraindications to terlipressin should not receive or would be unlikely to respond to other vasoconstrictors. (See 'Agents if terlipressin is unavailable or contraindicated' below.)

●Contraindications – Contraindications to terlipressin can be absolute or relative (table 1).  

•Absolute contraindications – Terlipressin should not be administered to patients with hypoxia (eg, SpO2 <90 percent on room air) or worsening respiratory symptoms, or to patients with a history of significant vascular disease or ongoing myocardial, peripheral, or mesenteric ischemia. In a trial in which 300 patients were randomized to terlipressin plus albumin or albumin alone, there were increased rates of respiratory failure and death related to respiratory failure in the terlipressin group (14 versus 5 percent, and 11 versus 2 percent, respectively) [9]. Although many cases of respiratory failure in this trial were related to aspiration pneumonia or bacterial pneumonia, there was an increased rate of pulmonary edema, likely precipitated by the increased cardiac afterload and decreased cardiac output induced by terlipressin therapy.

•Relative contraindications – We generally do not give terlipressin to patients with any of the following characteristics:

-Serum creatinine >5 mg/dL.

-Acute-on-chronic liver failure (ACLF) grade 3 (ie, ≥3 organ failures) [10] (table 2).

-Serum bilirubin >10 mg/dL. However, some experts do not have a bilirubin threshold for withholding terlipressin.

Patients with severe kidney or liver injury, or with grade 3 ACLF, are unlikely to respond to treatment with vasoconstrictor therapy [11-13]. In addition, patients with grade 3 ACLF have a high risk (30 percent) of developing terlipressin-associated respiratory failure [14].

●Dosing – Terlipressin may be administered in bolus form or as continuous therapy. In the United States, terlipressin has been approved for use in bolus form. However, continuous infusion may confer a lower rate of complications [15], most likely due to lower effective cumulative doses. Patients on terlipressin therapy should receive concomitant intravenous albumin (see 'Adjunctive albumin with vasoconstrictors' below) while being monitored for ischemic side effects, volume overload, and the development of respiratory failure (see 'Monitoring during treatment' below) [16].

Patients who have no response after three days of treatment should have terlipressin discontinued (see 'Duration of therapy' below) [16]. Terlipressin dosing is as follows [16]:

•For bolus dosing (algorithm 1), terlipressin acetate is administered intravenously (IV) at an initial dose of 1 mg every six hours. For patients with a partial but insufficient response (defined as <30 percent decrease in serum creatinine) after three days, the dose is increased to the maximum dose of 2 mg every six hours.

•For continuous infusion (algorithm 2), terlipressin acetate is administered IV at a dose of 2 mg per day. For patients with an insufficient response (defined as <25 percent decrease in serum creatinine) after two days, the dose is increased to 4 mg per day. For patients who have a partial but insufficient response after a total of four days of terlipressin, the daily dose can be increased further (not more frequently than every two days) in 2 mg increments to a maximum of 12 mg daily.

In the United States, terlipressin dosages are expressed as the amount of terlipressin, not the amount of terlipressin acetate. Terlipressin 0.85 mg is equivalent to terlipressin acetate 1 mg.

●Supporting evidence – Terlipressin is the preferred vasoconstrictor for the treatment of HRS-AKI because it is the most studied and consistently effective agent. The best efficacy data for terlipressin originate from four randomized trials of patients with HRS-AKI comparing terlipressin plus albumin with albumin alone [9,17-19]; the overall HRS-AKI reversal rate in most terlipressin trials is approximately 40 percent [20]. In the largest of these four trials, 300 patients with HRS-AKI were randomized in a 2:1 ratio to receive bolus dose terlipressin or placebo for up to 14 days [9]. Concomitant IV albumin, recommended for all patients, was administered to 83 percent of the terlipressin group and to 91 percent of the placebo group. Reversal of HRS-AKI, defined as an improvement of serum creatinine to 1.5 mg/dL or less, occurred in 78 patients (39 percent) in the terlipressin group and 18 (18 percent) in the placebo group.

Terlipressin has not been shown to improve overall transplant-free survival (see 'Prognosis' below). In post hoc analyses of trial data, terlipressin was associated with shorter lengths of stay in the intensive care unit and lower rates of kidney replacement therapy [21,22].

●Mechanism of action – Terlipressin is a prodrug of lysine vasopressin that acts on the V1 receptor of vascular smooth muscle cells. In the splanchnic circulation, terlipressin causes vasoconstriction in the mesenteric and gastric arteries, thereby reducing the inflow into the portal vein and reducing elevated portal pressure, which is a pivotal factor in the pathogenesis of HRS-AKI (see "Hepatorenal syndrome: Clinical presentation and diagnosis", section on 'Pathogenesis'). Within the liver, terlipressin reduces hepatic arterial resistance, and this results in intrahepatic vasodilatation and a further fall of the portal pressure by at least another 20 percent [23]. Some of the splanchnic circulatory volume is then re-distributed to the central circulation, indirectly reducing the activities of various endogenous vasoconstrictor systems such as the sympathetic nervous system and the renin-angiotensin-aldosterone system. This has the beneficial effect of reducing the severity of renal vasoconstriction. Terlipressin also increases systemic vascular resistance, and the consequent increase in mean arterial pressure leads to an increase in kidney perfusion pressure, further improving kidney blood flow [24].

Agents if terlipressin is unavailable or contraindicated

Norepinephrine for patients in the ICU — Although some investigators have used norepinephrine to treat HRS-AKI outside the intensive care unit (ICU) [25], norepinephrine administration typically requires transfer to the ICU.  

●Norepinephrine for select patients – Norepinephrine is a peripheral vasoconstrictor that acts on alpha-adrenergic receptors and is predominantly used to treat HRS-AKI when terlipressin is unavailable. Although terlipressin is generally our preferred vasoconstrictor for HRS-AKI (see 'Terlipressin preferred' above), we use norepinephrine rather than terlipressin in the following clinical scenarios:

•Critically ill patients who require vasopressor support.

•Patients eligible for liver transplantation who have hypoxia or respiratory distress. Patients treated with norepinephrine and albumin may be less likely to develop pulmonary edema than those treated with terlipressin and albumin because norepinephrine, in contrast to terlipressin, is a positive inotrope and does not cause pulmonary venoconstriction [5].

Except for hypoxia and respiratory distress, the absolute and relative contraindications to norepinephrine are the same as those for terlipressin. (See 'Terlipressin preferred' above.)

●Dosing – Norepinephrine is given via a central venous catheter as a continuous infusion (0.5 to 3 mg/hr), in conjunction with daily albumin (see 'Adjunctive albumin with vasoconstrictors' below), with the goal of raising the mean arterial pressure by >10 mmHg; however, we do not up-titrate norepinephrine in patients who develop elevated blood pressures. Patients treated with norepinephrine should be monitored for ischemic side effects and cardiac arrhythmias. (See 'Monitoring during treatment' below.)

●Supporting evidence – Existing data suggest that norepinephrine has similar efficacy to terlipressin for the treatment of HRS-AKI [26]. However, trials comparing the relative efficacy of norepinephrine to terlipressin are limited by small size and/or high risk of bias. In five such relative efficacy trials, the total number of included patients was just over 200 [27-31]. In one trial in which 120 patients with acute on chronic liver failure were randomized to norepinephrine or terlipressin, patients in the norepinephrine group had lower survival and higher rates of kidney replacement therapy [32]. However, this trial lacked blinding and patients were not required to have cirrhosis, a condition that is part of the diagnostic criteria for HRS-AKI. (See "Hepatorenal syndrome: Clinical presentation and diagnosis".)

Midodrine and octreotide for patients not in the ICU — The combination of midodrine and octreotide is used to treat HRS-AKI when terlipressin is unavailable and transfer to the ICU for norepinephrine therapy is either impossible or, as for patients ineligible for liver transplantation, not advised. Midodrine is an oral systemic vasoconstrictor that raises blood pressure and hence kidney perfusion pressure. Octreotide is a non-specific antagonist to various splanchnic vasodilators and therefore can reduce the extent of splanchnic arterial vasodilation that underlies the pathogenesis of HRS-AKI (see "Hepatorenal syndrome: Clinical presentation and diagnosis", section on 'Pathogenesis').

Midodrine is given orally (starting at 7.5 to 10 mg and increasing the dose at eight-hour intervals up to a maximum of 30 mg by mouth three times daily) and octreotide is either given as a continuous intravenous infusion (50 mcg/hr) or subcutaneously (100 to 200 mcg three times daily). The midodrine dose should be increased with each consecutive dose in order to achieve a rapid increase in mean arterial pressure (ideally >10 mmHg); however, we do not up-titrate midodrine in patients who develop elevated blood pressure. Albumin is given in conjunction with midodrine and octreotide. (See 'Adjunctive albumin with vasoconstrictors' below.)

Data supporting the use of midodrine and octreotide for the treatment of HRS-AKI are sparse, derived from case series or small retrospective studies [33,34]. A network meta-analysis suggested that midodrine and octreotide therapy may not be superior to placebo [35]. In a randomized trial, combination therapy with midodrine and octreotide was significantly inferior to terlipressin in reversing HRS-AKI [36]. However, this trial was small (n = 49) and the maximum midodrine dose was less than half that typically employed in clinical practice.

Adjunctive albumin with vasoconstrictors — For patients with HRS-AKI who do not have evidence of intravascular volume overload, we administer 20 or 25 percent albumin intravenously (20 to 40 grams daily) in conjunction with vasoconstrictor therapy. However, the optimal dose of albumin in this setting is unclear [4,6,37]. We base albumin dosing on the patient’s volume status. We use higher doses of albumin (eg, 40 grams) for most patients, but lower doses (eg, 20 grams) for patients who appear at risk of developing intravascular volume overload. Albumin should be discontinued in patients who have evidence of intravascular volume overload and/or pulmonary edema.

The primary risk of albumin administration in hospitalized patients with cirrhosis is volume overload [9,38,39], though in patients with HRS-AKI this risk may be less when albumin is used with norepinephrine rather than with terlipressin (see 'Agents if terlipressin is unavailable or contraindicated' above). The risk of albumin-associated pulmonary edema is likely greatest in patients with the greatest severity of illness. In the largest trial comparing terlipressin plus albumin with albumin alone (n = 300) for the treatment of HRS-AKI, respiratory failure predominantly occurred in patients with grade 3 acute on chronic liver failure (ie, ≥3 organ failures) [9] (table 2).

The rationale for using albumin as an adjunct to vasoconstrictor therapy for the treatment of HRS-AKI is predominantly physiologic. Albumin is an effective volume expander and also has antiinflammatory, antioxidant, immune modulatory and endothelial stabilizing properties [40]. Therefore, albumin use in patients with HRS-AKI is expected to improve the mismatch between circulatory capacitance and intravascular volume and also reduce the inflammation that contributes to the pathophysiology of HRS-AKI (see "Hepatorenal syndrome: Clinical presentation and diagnosis", section on 'Pathogenesis'). In a post hoc analysis of two randomized trials comparing terlipressin plus albumin versus albumin alone for the treatment of HRS-AKI, a higher albumin dose was associated with higher 90-day survival [41]. However, this study did not identify an optimal dose of albumin.

Monitoring during treatment — In addition to the clinical and laboratory parameters monitored in all patients with AKI (see "Overview of the management of acute kidney injury (AKI) in adults"), we monitor the following in patients undergoing treatment for HRS-AKI:

●Adverse effects of vasoconstrictor therapy

•Vasoconstrictor administration can lead to myocardial, peripheral, or mesenteric ischemia. Serious ischemic events warrant discontinuation of vasoconstrictor therapy.

•Common side effects of terlipressin include abdominal pain and diarrhea, which are caused by reduced mesenteric blood flow. These side effects can be mitigated by dose reduction or changing from bolus to continuous dosing. (See 'Terlipressin preferred' above.)

•Patients on norepinephrine should be monitored for the development of cardiac arrhythmias, which may limit dose escalation. Most institutions require norepinephrine to be administered in the ICU, where cardiac telemetry monitoring is routine.

●Volume status – Monitoring volume status is critical to avoiding volume overload and treatment-associated respiratory failure. Some clinicians use point-of-care ultrasound to augment their clinical assessment of volume status in this setting [42,43].

•Albumin infusion should be discontinued in patients with evidence of intravascular volume overload and/or pulmonary edema.

•Terlipressin should not be administered to patients with hypoxia (eg, SpO2 <90 percent on room air) or worsening respiratory symptoms; such patients are sometimes treated with norepinephrine rather than terlipressin. (See 'Agents if terlipressin is unavailable or contraindicated' above.)

Duration of therapy — We treat with vasoconstrictor and albumin therapy for a maximum of 14 days. We discontinue vasoconstrictor and albumin therapy in patients with HRS-AKI who meet any of the following criteria during treatment [5]:

●No improvement in serum creatinine after three days of therapy

●Serum creatinine improved to within 0.3 mg/dL of baseline

●Serious adverse reaction

●Initiation of kidney replacement therapy

●Liver transplantation

●Total duration of therapy 14 days

PATIENTS WHO DO NOT RESPOND TO MEDICAL THERAPY — 

Kidney replacement therapy (KRT) is an option for some patients who do not respond to medical therapy for hepatorenal syndrome-acute kidney injury (HRS-AKI). The indications for and modality of KRT in AKI are discussed separately. (See "Kidney replacement therapy (dialysis) in acute kidney injury in adults: Indications, timing, and dialysis dose".)

Limited use of kidney replacement therapy — For patients with HRS-AKI who do not respond to medical therapy, we generally limit the use of KRT to patients who are candidates for liver transplantation. Unless used as a bridge to liver transplant, patients with HRS-AKI who initiate KRT have a dismal prognosis (see 'Prognosis' below) [44-47]. Furthermore, KRT in this setting is associated with high rates of complications such as intradialytic hypotension, adverse cardiac events, and access-related bleeding and infection.

Avoidance of transjugular intrahepatic portosystemic shunt — We do not use transjugular intrahepatic portosystemic shunt (TIPS) to treat HRS-AKI. No high-quality data demonstrate that TIPS is an effective therapy for HRS-AKI, and TIPS has potentially severe complications including procedure-associated bleeding, an increase in hepatic encephalopathy, and worsening of kidney and liver function [48].

Insertion of a TIPS results in a rapid reduction in portal pressure, followed by a significant increase in venous return and cardiac output [49]. The systemic circulation vasodilates to accommodate the high volume of venous return from the splanchnic to the systemic circulation. The systemic vascular resistance falls significantly after TIPS insertion, and this may compromise kidney perfusion and worsen kidney function [50]. In addition, the rapid shunting of blood through the liver also makes the liver parenchyma relatively ischemic. Thus, in a patient with advanced liver dysfunction, liver failure could ensue.

LIVER TRANSPLANTATION — 

Unless there are contraindications, patients with hepatorenal syndrome-acute kidney injury (HRS-AKI) should be referred for consideration for a liver transplant. Liver transplantation is the definitive treatment for HRS-AKI because it corrects the underlying pathophysiology of liver failure and portal hypertension.

There has been some controversy regarding the use of vasoconstrictors to treat HRS-AKI in the pretransplant period, as a positive response to vasoconstrictor therapy will lead to a reduction in the serum creatinine, and therefore a reduction in Model for End-stage Liver Disease (MELD) score that will lower the priority for liver transplant (see "Model for End-stage Liver Disease (MELD)"). However, response to vasoconstrictor treatment is associated with improved transplant-free survival despite a longer wait time for liver transplantation, as well as a lower risk of developing post-transplant chronic kidney disease [51]. In a study that provided terlipressin to 50 patients with HRS-AKI who were eligible for liver transplantation, 10 of 16 patients (63 percent) who responded to terlipressin received a liver transplant, suggesting that treatment with terlipressin does not reduce the rate of subsequent liver transplantation [52]. Of note, several liver transplant programs in Europe have practiced locking the pre-terlipressin MELD score in their calculation of the patient’s priority for liver transplant [53]. This ensures equity in the allocation of organs for wait-listed patients and removes pharmacotherapy as a complicating factor.

PROGNOSIS — 

The survival of patients with untreated hepatorenal syndrome-acute kidney injury (HRS-AKI) is usually measured in days to weeks [54]. For patients with treated HRS-AKI, the prognosis depends on liver transplantation:

●For patients who receive a liver transplant, survival is excellent and similar to that of patients who receive a liver transplant but do not have HRS-AKI [55].

●For patients who do not receive a liver transplant, the prognosis of HRS-AKI is poor [47,56,57], as illustrated by the following data:

•In a study of over 2000 hospitalized patients with cirrhosis and acute kidney injury, the 90-day mortality of patients with HRS-AKI and acute tubular necrosis was 49 percent and 53 percent, respectively [56].

•In another study of 472 patients with cirrhosis and acute kidney injury who were initiated on hemodialysis or continuous renal replacement therapy, only 15 percent of patients not listed for liver transplant were alive after six months [47]. The median survival was 21 days for those diagnosed with HRS-AKI and 12 days for those diagnosed with acute tubular necrosis.

The use of terlipressin does not impact the overall transplant-free survival in patients with HRS-AKI [9], but the prognosis of patients who respond to terlipressin is better than that of patients who do not. In a trial that included 78 patients with HRS-AKI treated with either continuous or bolus terlipressin dosing, the 90-day transplant-free survival in patients who responded to terlipressin compared with that in patients who did not respond was 70 percent and 41 percent, respectively [15].

Despite the poor prognosis of patients with HRS-AKI, palliative care is underutilized in this setting. In the United States, less than 30 percent of patients with a diagnosis of HRS-AKI receive palliative care [58], which is associated with lower rates of mechanical ventilation, blood product transfusion, paracentesis, and kidney replacement therapy [59].

PREVENTION — 

Hepatorenal syndrome-acute kidney injury (HRS-AKI) may be prevented by avoiding a precipitating event (see "Hepatorenal syndrome: Clinical presentation and diagnosis", section on 'Precipitants'). As such, measures to prevent HRS-AKI include the following:

●Regular monitoring of kidney function in patients on diuretics. (See "Ascites in adults with cirrhosis: Initial therapy".)

●Avoidance of overly aggressive diuretic or lactulose therapy.

●Appropriate use of intravenous albumin infusion in the setting of large-volume paracentesis. (See "Ascites in adults with cirrhosis: Diuretic-resistant ascites".)

●Prompt treatment of spontaneous bacterial peritonitis (SBP) and other infections. (See "Spontaneous bacterial peritonitis in adults: Treatment and prophylaxis", section on 'Treatment'.)

●Appropriate SBP prophylaxis. (See "Spontaneous bacterial peritonitis in adults: Treatment and prophylaxis", section on 'Prophylaxis'.)

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cirrhosis" and "Society guideline links: Acute kidney injury in adults".)

SUMMARY AND RECOMMENDATIONS

●General measures – In addition to the general measures applicable to all patients with acute kidney injury (AKI), such as avoidance of hypotension and nephrotoxins (see "Overview of the management of acute kidney injury (AKI) in adults"), general measures for patients with hepatorenal syndrome-AKI (HRS-AKI) include a search for and treatment of HRS-AKI precipitants. We promptly evaluate and treat potential sources of infection, maintain adequate intravascular volume, and typically stop beta-blocker therapy in patients with HRS-AKI. (See 'General measures in all patients' above.)

●Medical therapy – The definitive treatment for hepatorenal syndrome-acute kidney injury (HRS-AKI) is a liver transplant, not medical therapy. Vasoconstrictors and adjunctive intravenous albumin are best used as a bridge to liver transplantation. (See 'Medical therapy' above.)

•Vasoconstrictors – Vasoconstrictor therapy is the mainstay of medical treatment for HRS-AKI. (See 'Vasoconstrictors' above.)

-For most patients with HRS-AKI, we suggest terlipressin rather than norepinephrine, midodrine plus octreotide, or other vasoconstrictors (Grade 2C). Contraindications to terlipressin can be absolute or relative (table 1 and table 2). Terlipressin may be administered in bolus form or as continuous therapy. (See 'Terlipressin preferred' above.)

-The main reason to use alternative vasoconstrictor therapies such as norepinephrine or midodrine plus octreotide is unavailability of terlipressin. Most patients with HRS-AKI who have absolute or relative contraindications to terlipressin should not receive or would be unlikely to respond to other vasoconstrictors. Although terlipressin is generally our preferred vasoconstrictor for HRS-AKI, we use norepinephrine in critically ill patients who require vasopressor support and in patients eligible for liver transplantation who have hypoxia or respiratory distress. (See 'Agents if terlipressin is unavailable or contraindicated' above and 'Norepinephrine for patients in the ICU' above.)

•Adjunctive albumin with vasoconstrictor therapy – For most patients with HRS-AKI who are treated with vasoconstrictor therapy, we suggest concomitant intravenous albumin (Grade 2C). Albumin should not be administered to patients who have evidence of intravascular volume overload and/or pulmonary edema. (See 'Adjunctive albumin with vasoconstrictors' above.)

•Monitoring during treatment – In addition to the clinical and laboratory parameters monitored in all patients with AKI (see "Overview of the management of acute kidney injury (AKI) in adults"), we monitor volume status and for adverse effects of vasoconstrictor therapy. Monitoring volume status is critical to avoiding volume overload and treatment-associated respiratory failure. (See 'Monitoring during treatment' above.)

•Duration of therapy – We treat with vasoconstrictor and albumin therapy for a maximum of 14 days. We discontinue vasoconstrictor and albumin therapy in patients with HRS-AKI who meet any of the following criteria during treatment (see 'Duration of therapy' above):

-No improvement in serum creatinine after three days of therapy

-Serum creatinine improved to within 0.3 mg/dL of baseline

-Serious adverse reaction

-Initiation of kidney replacement therapy

-Liver transplantation

-Total duration of therapy 14 days

●Patients who do not respond to medical therapy – For patients with HRS-AKI who do not respond to medical therapy, we generally limit the use of kidney replacement therapy (KRT) to patients who are candidates for liver transplantation. KRT in this setting is associated with a high rate of complications. (See 'Patients who do not respond to medical therapy' above.)

●Prognosis – The survival of patients with untreated hepatorenal syndrome-acute kidney injury (HRS-AKI) is usually measured in days to weeks. For patients with treated HRS-AKI, the prognosis depends on liver transplantation. (see 'Prognosis' above)

ACKNOWLEDGMENT — 

The UpToDate editorial staff acknowledges Bruce A Runyon, MD, FAASLD, who contributed to an earlier version of this topic review.