Can Lasix (furosemide) be administered in hepatorenal syndrome with acute kidney injury (AKI)?

From the Guidelines

Lasix (furosemide) is generally not recommended in hepatorenal syndrome (HRS) with acute kidney injury (AKI). HRS is characterized by functional renal failure in patients with advanced liver disease, where the kidneys are structurally normal but undergo intense vasoconstriction. Using loop diuretics like Lasix in this setting can worsen the situation by further reducing intravascular volume, exacerbating renal hypoperfusion, and potentially accelerating kidney injury.

The primary treatment approach for HRS-AKI should instead focus on addressing the underlying pathophysiology through vasoconstrictors (like norepinephrine, terlipressin, or midodrine plus octreotide) combined with albumin to improve effective arterial blood volume and renal perfusion, as recommended by the American Society of Transplantation liver and intestine community of practice 1.

Some key points to consider in the management of HRS-AKI include:

• Diagnosing the etiology of AKI is critical in determining therapy 1
• Removing potential precipitating factors such as diuretics and optimizing volume status should be initiated even before a cause of AKI is established 1
• Vasoconstrictor therapy, such as terlipressin, has been shown to improve kidney function and short-term survival benefit in patients with HRS-AKI 1
• Albumin should be used in combination with vasoconstrictors to improve effective arterial blood volume and renal perfusion 1

In some cases, if the patient has significant volume overload alongside HRS, very careful use of diuretics might be considered under close monitoring, but this should be approached with extreme caution and is generally avoided in the initial management, as suggested by the KDIGO practice guideline on acute kidney injury 1. The fundamental issue in HRS is not fluid retention that would respond to diuretics, but rather a profound disturbance in circulatory function requiring restoration of renal blood flow.

From the FDA Drug Label

In patients with hepatic cirrhosis and ascites, Furosemide tablets therapy is best initiated in the hospital. If increasing azotemia and oliguria occur during treatment of severe progressive renal disease, Furosemide tablets should be discontinued.

The use of Furosemide in hepatorenal syndrome with AKI is not directly addressed in the label. However, it does mention that in patients with hepatic cirrhosis and ascites, therapy should be initiated in the hospital, and if increasing azotemia and oliguria occur, the drug should be discontinued.

• The label warns against using the drug in cases of severe progressive renal disease.
• It is recommended to exercise caution and consider the potential risks of ototoxicity and electrolyte depletion. Given the potential risks and the fact that the label does not provide clear guidance on the use of Furosemide in hepatorenal syndrome with AKI, a conservative approach would be to avoid its use in this setting or to use it with extreme caution and close monitoring, ideally in a hospital setting 2.

From the Research

Hepatorenal Syndrome with AKI and Lasix Administration

• There is no direct evidence in the provided studies to support the administration of Lasix in hepatorenal syndrome with acute kidney injury (AKI) [ 3, 4, 5, 6, 7 ].
• The mainstay of therapy for HRS-AKI is a vasoconstrictor (terlipressin or norepinephrine) combined with albumin, which achieves resolution of HRS in 40-50% of cases [ 3 ].
• Terlipressin with albumin has shown mixed results for complete HRS-AKI reversal with no reductions in crude mortality but adverse effect concerns involving ischemic and pulmonary events [ 7 ].
• Liver transplantation is the only option for patients failing to respond to medical therapies [ 3, 5 ].
• The use of diuretics like Lasix is not mentioned as a treatment option for HRS-AKI in the provided studies, suggesting that it may not be a recommended treatment for this condition [ 3, 4, 5, 6, 7 ].

Treatment Options for HRS-AKI

• Vasoconstrictors such as terlipressin or norepinephrine are used in combination with albumin to treat HRS-AKI [ 3, 4, 5, 7 ].
• Midodrine with octreotide and albumin is less effective than terlipressin but better than albumin alone at improving 30-day mortality [ 4 ].
• Liver transplantation is the ultimate treatment option for HRS-AKI [ 3, 5, 6 ].

Diagnosis and Challenges of HRS-AKI

• HRS-AKI is a diagnosis of exclusion and portends a poor prognosis, with upward of 80% mortality at 2 weeks without treatment [ 4 ].
• Diagnostic criteria for HRS have been developed and were recently modified, but diagnosing HRS and differentiating it from other causes of AKI in cirrhotic patients continues to be a difficult task in some patients [ 6, 7 ].