Current Pharmacologic Therapies for Hepatorenal Syndrome-Acute Kidney Injury

BACKGROUND & AIMS: Hepatorenal syndrome (HRS) can occur in patients with cirrhosis and ascites due to splanchnic vasodilation, renal hypoperfusion, and vasoconstriction. HRS is a diagnosis of exclusion and portends a poor prognosis, with upward of 80% mortality at 2 weeks without treatment. This review will highlight randomized controlled trials for HRS pharmacotherapy. METHODS: A PubMed review of randomized controlled trials conducted over the past 25 years was undertaken; 18 studies were included. RESULTS: Initial studies showed that norepinephrine is as effective as terlipressin for HRS reversal. Midodrine with octreotide and albumin is less effective than terlipressin but better than albumin alone at improving 30-day mortality. Recently, terlipressin with albumin led to significantly higher rates of HRS reversal compared to albumin alone. Non-response to terlipressin can predict 90-day mortality in acute-on-chronic-liver failure. CONCLUSIONS: Our current understanding of HRS treatment is improved by recent randomized clinical trials. Previous studies using varying medication doses along with the "old" definition of hepatorenal syndrome (HRS type 1) rather than HRS-AKI means that there is still a need for future multi-center prospective studies further refining the risk-benefit ratio of vasoconstrictors for HRS-AKI patients. The Food and Drug Administration has approved terlipressin for use in September 2022. Because it will take time to adapt into clinical practice, less cost-prohibitive vasoconstrictors should still be considered. Opportunities also exist to clarify the safety, timing of initiation, as well as possible discontinuation of terlipressin.