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Kidney Week

Abstract: FR-PO0119

Adverse Events in Real-World Terlipressin Use: Results from the HRS-HARMONY Consortium

Session Information

Category: Acute Kidney Injury

  • 102 AKI: Clinical, Outcomes, and Trials

Authors

  • Allegretti, Andrew S., Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Robinson, Jevon E., Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Ouyang, Tianqi, Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Patidar, Kavish Rohit, Division of Gastroenterology and Hepatology, Department of Medicine, Lynda K. and David M. Underwood Center for Digestive Disorders, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist Hospital, Houston, Texas, United States

Group or Team Name

  • HRS-HARMONY Consortium.
Background

Terlipressin became the first FDA-approved therapy for hepatorenal syndrome-acute kidney injury (HRS-AKI) in September 2022. We present its initial safety experience at 16 U.S. academic medical centers.

Methods

Consecutive patients with HRS-AKI treated with terlipressin through 5/2024 were followed for 90 days. Adverse events (AEs) leading to terlipressin discontinuation were evaluated daily, including respiratory failure (defined as new oxygen requirement). AEs were analyzed by Standard Criteria (SC, conforming to the FDA label) vs. Extended Criteria (EC, acute on chronic liver failure [ACLF] grade 3, sCr >5 mg/dL, or hypoxia at time of initiation), Overall Response (improvement in at least 1 AKI stage or to ≤0.3 mg/dL of baseline sCr) vs not, bolus vs continuous dosing, and MELD score ≤35 vs >35.

Results

243 patients were analyzed: median age 58 years, 60% male, 56% alcohol-associated cirrhosis, sCr at initiation 2.79 [IQR 2.27, 3.57] mg/dL, MELD 31 [26, 37]. 15% were treated with continuous dosing; 41% died and 28% received liver transplant. Patients received 200 [125, 350] g albumin prior to initiation and 63 [0, 125] g while on drug. 54% met EC, most commonly due to ACLF grade 3 (45%). Overall Response occurred in 55% (58% continuous vs 55% bolus, p = 0.81). Overall AE rate was 17% (Table). AEs were more common in No Response (24% vs 12%, p = 0.02), EC (23% vs 12%, p = 0.04), ACLF grade 3 (23% vs 13%, p = 0.04), MELD >35 (20% vs. 14%, p = 0.27), and bolus dosing (18% vs 11%, p= 0.35). Respiratory failure occurred in 10% and was more common in No Response (13% vs 7%, p = 0.16), EC (13% vs 6%, p = 0.06), ACLF grade 3 (13% vs 7%, p = 0.13), but not bolus dosing (9% vs 11%, p = 0.76).

Conclusion

AEs, including respiratory failure, were more common when terlipressin was used outside FDA label guidance. Continuous dosing requires larger studies but showed a trend towards fewer non-respiratory AEs.

 Overall Standard CriteriaExtended CriteriaP value BolusContinuousP value
n (%)243 112131  20736 
Any Adverse Event42 (17.3) 15 (12.1)27 (22.7)0.044 38 (18.4)4 (11.1)0.348
Abdominal Pain8 (3.3) 4 (3.2)4 (3.4)1 8 (3.9)0 (0.0)0.609
Nausea6 (2.5) 3 (2.4)3 (2.5)1 6 (2.9)0 (0.0)0.596
Diarrhea3 (1.2) 2 (1.6)1 (0.8)1 3 (1.4)0 (0.0)1
Bradycardia6 (2.5) 3 (2.4)3 (2.5)1 6 (2.9)0 (0.0)0.596
Ischemia3 (1.2) 1 (0.8)2 (1.7)0.616 3 (1.4)0 (0.0)1
Respiratory Failure23 (9.5) 7 (5.6)16 (13.4)0.063 19 (9.2)4 (11.1)0.757

Funding

  • NIDDK Support

Digital Object Identifier (DOI)