Safety and efficacy of continuous terlipressin infusion in HRS-AKI in a transplant population

Author:

Reddy K. Rajender1ORCID,Weinberg Ethan M.1ORCID,Gonzalez Stevan A.2ORCID,Izzy Manhal J.3ORCID,Simonetto Douglas A.4ORCID,Frederick R. Todd5ORCID,Rubin Raymond A.6ORCID,Fricker Zachary7ORCID,Ikahihifo-Bender Jade1ORCID,Harte Maggie1ORCID,Garcia Sandra2,Campbell Kathryn3,Olofson Amy4ORCID,Razavi Ryan F.5,James Janelle M.6,Patel Het7,Kim-Lee Grace1ORCID,Witkiewicz Sherry8ORCID,Tobin William8,Jamil Khurram9ORCID

Affiliation:

1. Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA

2. Division of Hepatology, Department of Medicine, Simmons Transplant Institute, Baylor Scott & White All Saints Medical Center, Fort Worth, Texas, USA

3. Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA

4. Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA

5. Division of Hepatology, Department of Advanced Organ Therapies and Transplantation, California Pacific Medical Center, San Francisco, California, USA

6. Department of Transplantation, Piedmont Transplant Institute, Piedmont Healthcare, Atlanta, Georgia, USA

7. Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA

8. International HealthCare, LLC, Norwalk, Connecticut, USA

9. Formerly at Department of Research & Development, Mallinckrodt Pharmaceuticals, Scientific Affairs, Bridgewater, New Jersey, USA

Abstract

Hepatorenal syndrome-acute kidney injury (HRS-AKI) is associated with significant morbidity and mortality. While liver transplantation is the definitive treatment, continuous terlipressin infusion for HRS-AKI may provide benefit and, as such, was assessed in a population composed of candidates for liver transplant (LT). Fifty hospitalized LT-eligible patients with HRS-AKI received a single bolus followed by continuous terlipressin infusion. Acute-on-chronic liver failure grade 3, serum creatinine (SCr)>5.0 mg/dL, or Model for End-Stage Liver Disease (MELD) ≥35 were exclusions. Fifty hospitalized patients who received midodrine and octreotide or norepinephrine for HRS-AKI served as a historical comparator cohort. Complete response (CR) was defined as a ≥30% decrease in SCr with end-of-treatment (EOT) SCr≤1.5, partial response as a ≥30% decrease in SCr with EOT SCr>1.5, and nonresponse as a <30% decrease in SCr. CR rate was significantly higher in the terlipressin cohort compared to the historical cohort (64% vs. 16%, p<0.001). Survival, while numerically higher in those who received terlipressin, was statistically similar (D30: 94% vs. 82%, p=0.12; D90: 78% vs. 68%, p=0.37). Renal replacement therapy (RRT) was more common among terlipressin NR than CR and PR (70% vs. 3% vs. 13%, p < 0.001). EOT MELD and SCr were significantly lower within terlipressin cohort (MELD: 19 vs. 25, SCr: 1.4 vs. 2.1 mg/dL, p<0.001). Sixteen of 40 terlipressin-treated patients received LT-alone (terlipressin CR in 10/16). One patient on terlipressin had a hypoxic respiratory failure that responded to diuretics; one possibly had drug-related rash. With continuous terlipressin infusion, a CR rate of 64% was observed with a favorable safety profile. Terlipressin use was associated with lower EOT MELD and SCr than the historical midodrine and octreotide/norepinephrine cohort; LT-alone was accomplished in a high proportion of complete terlipressin responders.

Publisher

Ovid Technologies (Wolters Kluwer Health)

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