What is the relationship between Acute Kidney Injury (AKI) and hepatorenal syndrome?

From the Guidelines

Acute kidney injury (AKI) in hepatorenal syndrome (HRS) requires prompt management with volume expansion using albumin as the first-line therapy, followed by the use of vasoconstrictors such as terlipressin or norepinephrine, as these interventions have been shown to improve morbidity, mortality, and quality of life outcomes. The recommended initial approach for patients with cirrhosis presenting with AKI and evidence of intravascular volume depletion includes a trial of volume expansion with albumin at a dose of 1 g/kg of body weight daily for 2 consecutive days (with a cap of 100 g/d) 1. This is based on the fact that, in cirrhosis with ascites, albumin is more effective in restoring effective arterial blood volume than saline solution.

Key Considerations

• The use of albumin should be tailored to the volume status of the patient, although the best method to assess volume is still unknown 1.
• Vasoactive drugs (terlipressin, NE, or combination of octreotide/midodrine) should be used in the treatment of HRS-AKI but not in other forms of AKI in cirrhosis, as they can help counteract splanchnic vasodilation and improve effective arterial blood volume, thereby enhancing renal perfusion 1.
• Liver transplantation is the most effective treatment for HRS-AKI, and pharmacotherapy for HRS-AKI before proceeding with liver transplantation may be associated with better post-liver transplantation outcomes 1.

Treatment Approach

• The initial management should focus on volume expansion with albumin, followed by the use of vasoconstrictors if there is evidence of HRS-AKI.
• Patients should also receive supportive care including careful fluid management, avoidance of nephrotoxic drugs, and treatment of underlying liver disease.
• Diuretics should be discontinued during acute treatment.
• If medical therapy fails, liver transplantation evaluation should be expedited as it represents the definitive treatment for hepatorenal syndrome, with pre-transplant dialysis considered as a bridge in severe cases.

From the Research

Definition and Pathophysiology of Hepatorenal Syndrome

• Hepatorenal syndrome (HRS) is a primarily functional form of acute kidney injury (AKI) that develops in patients with decompensated cirrhosis 2.
• The pathophysiologic cascade that leads to HRS begins with pooling of blood in the splanchnic system, resulting in a decrease in effective circulating arterial volume 2.
• HRS-AKI occurs in the setting of advanced chronic liver disease, portal hypertension, and ascites, and is found in ∼20% of patients presenting to the hospital with AKI 3.

Diagnosis and Treatment of Hepatorenal Syndrome

• The diagnosis of HRS-AKI can be challenging, but novel biomarkers such as urinary neutrophil gelatinase-associated lipocalin may be useful 3.
• The mainstay of therapy is a vasoconstrictor (terlipressin or norepinephrine) combined with albumin, which achieves resolution of HRS in 40-50% of cases 3.
• Terlipressin plus albumin is significantly more effective than midodrine and octreotide plus albumin in improving renal function in patients with HRS 4.
• The combination of octreotide, midodrine, and albumin has shown possible benefit in small preliminary studies in improving renal function and short-term survival 5.

Treatment Outcomes and Prognosis

• Liver transplantation is the ultimate solution for patients with HRS-AKI, but is only an option in a minority of patients due to contraindications and limited organ availability 6.
• Renal replacement therapy is a temporary option, but confers an extremely poor short-term prognosis in patients with HRS-AKI 6.
• Early diagnosis and initiation of HRS-AKI-specific treatment can improve outcomes, and improvement in renal function and lower baseline Model for End-Stage Liver Disease score are associated with better survival 4, 3.