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Treating HRS-AKI

HRS, hepatorenal syndrome
Vasoconstrictors, in combination with albumin, are effective in improving kidney function in patients with HRS-AKI. The vasoconstrictor of choice for HRS-AKI is terlipressin. In settings where terlipressin is not available, norepinephrine should be considered, typically in an intensive care setting. If neither can be administered, a trial of oral midodrine in combination with octreotide may be considered, but its efficacy is low. All vasoconstrictors should be dosed according to the table; albumin 25% should be administered in combination with each vasoconstrictor and dosed according to clinical parameters. Response to vasoconstrictor therapy is defined by SCr decreasing to < 1.5 mg/dL or returning to within 0.3 mg/dL of baseline over a maximum of 14 days. In patients whose SCr remains at or above the pretreatment level over 4 days with the maximum tolerated doses of the vasoconstrictor, therapy may be discontinued. Disease may recur after discontinuation of treatment, so close follow-up is warranted. If there is recurrence, patients should be retreated.
Patients with HRS-AKI have a better response to therapy if therapy is started earlier rather than later. Terlipressin, when available, should be considered the treatment of choice as response rates are better than the poor response rates of midodrine, octreotide, and albumin.
Drug
Dosing and Administration
Terlipressin
Vasoconstrictor of choice for treating HRS-AKI*
Norepinephrine
Continuous IV infusion starting at 0.5 mg/h to achieve an increase in mean arterial pressure of at least 10 mmHg or an increase in urine output of > 200 mL/4 h

If at least one of these goals is not achieved, increase every 4 h in increments of 0.5 mg/h up to a maximum of 3 mg/h
Oral midodrine in combination with octreotide
Midodrine 5-15 mg po every 8 h
Octreotide 100-200 µg every 8 h or 50 µg/h via IV
*Terlipressin is currently an investigational agent being evaluated for the treatment of HRS in the U.S., and its safety and effectiveness have not yet been established by the FDA.
AKI, acute kidney injury; HRS, hepatorenal syndrome
Patients on vasoconstrictors and albumin should be closely monitored for the possible development of adverse effects. Adverse effects are infrequent, are mainly related to vasoconstrictors, and include hypertension, peripheral ischemia, abdominal pain, nausea, diarrhea, headache, intestinal ischemia, and cardiac ischemia. Pulmonary edema may develop from fluid overload related to albumin infusion. Early intervention may prevent more serious consequences, and most resolve after dose reduction or discontinuation of therapy.
Additional Special Considerations in HRS Management
Transplantation
All patients with cirrhosis and AKI should be considered for urgent liver transplant (LT) evaluation given the high short-term mortality even in responders to vasoconstrictors.
Simultaneous liver-kidney transplantation may be necessary for patients who are not expected to recover kidney function following transplantation.
Renal Replacement Therapy (RRT)
Use RRT in candidates for LT with worsening renal function, electrolyte disturbances, or increasing volume overload unresponsive to vasoconstrictor therapy.

Initiation of RRT in patients who are not candidates for LT must be made after defining goals of care with the patient and their family.
Multidisciplinary Teams
Given the complexity of cases of patients with suspected HRS-AKI, decisions about management should be made by multidisciplinary teams.

Teams should include specialists in hepatology, nephrology, critical care, and transplant surgery.
AKI, acute kidney injury; HRS, hepatorenal syndrome

The full HRS diagnostic algorithm is shown here:

The CLDF would like to thank David Bernstein, MD, Sammy Saab, MD, MPH, and Steven Flamm, MD, for their expertise and guidance in developing this document.

The citation for the published AASLD guidance is Biggins SW, Angeli P, Garcia-Tsao G, et al. Diagnosis, Evaluation, and Management of Ascites, Spontaneous Bacterial Peritonitis, and Hepatorenal Syndrome: 2021 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2021;74:1014-1048. DOI: 10.1002/hep.31884. PMID: 33942342