Terlipressin in the management of adults with hepatorenal syndrome-acute kidney injury (HRS-AKI)

ABSTRACT

Introduction

Kidney is the most common extra-hepatic organ involved in patients with advanced liver cirrhosis and acute-on-chronic liver failure. Hepatorenal syndrome-acute kidney injury (HRS-AKI) accounts for most hospitalizations, and liver transplantation (LT) remains the ultimate and long-term treatment in such patients. However, HRS-AKI, being a functional renal failure, has a fair chance of reversal, and as such, patients who achieve reversal of HRS-AKI have better outcomes post-LT.

Areas covered

In this review, we discuss the pharmacokinetics, pharmacodynamics and evidence to support the use of terlipressin in HRS-AKI while we also address predictors of response and the associated adverse events. Further, we discuss the role of terlipressin in the context of LT.

Expert opinion

The recommended treatment for HRS-AKI reversal includes a vasoconstrictor in addition to volume expansion with albumin. The three vasoconstrictor regimens generally used to treat HRS-AKI include octreotide plus midodrine, noradrenaline, and terlipressin. Of these, terlipressin is a widely used drug and has been recently approved by US Food and Drug Administration (USFDA) for HRS-AKI. Terlipressin is the most effective drug for HRS-AKI reversal and is associated with a decreased need for renal replacement therapy pre- and post-transplant. Furthermore, terlipressin responders have improved transplant-free and post-transplant survival.

KEYWORDS:

• Vasoconstrictors
• liver transplantation
• adverse events
• creatinine
• terlipressin
• midodrine
• octreotide
• noradrenaline

Article highlights

• Hepatorenal syndrome-acute kidney injury (HRS-AKI) is reported in up to 15–20% of hospitalized patients with cirrhosis and is associated with high mortality.

• Terlipressin is a prodrug and has been approved for treatment of HRS-AKI.

• Terlipressin has high efficacy in HRS-AKI reversal.

• Common adverse events of terlipressin include abdominal pain and diarrhea while less common and serious adverse events are myocardial ischemia and respiratory failure.

• Terlipressin non-responders prior to liver transplantation (LT) have a higher incidence of chronic kidney disease, prolonged need for renal replacement therapy and higher mortality post-LT.

Declaration of interests

This manuscript did not receive any funding. KRR serves on the Advisory Board of Mallinckrodt and receives research support (Paid to the University of Pennsylvania) from Mallinckrodt, Bio Vie, Grifols, and Sequana. AVK and JL have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Scientific accuracy review

BioVie provided a scientific accuracy review at the request of the journal editor.

Additional information

Funding

This paper was not funded.