Kidney Week

Abstract: FR-OR01

Terlipressin Improves Renal Replacement Therapy–Free Survival in Hepatorenal Syndrome Type 1

Session Information

• AKI Predictors and Outcomes: Research Abstracts
  October 23, 2020 | Location: Simulive
  Abstract Time: 05:00 PM - 07:00 PM

Category: Acute Kidney Injury

• 102 AKI: Clinical, Outcomes, and Trials

Authors

• Velez, Juan Carlos Q., Ochsner Health System, New Orleans, Louisiana, United States

Juan Carlos Q. Velez, MD, FASN



Dr. Juan Carlos Q. Velez earned a medical degree from Universidad Peruana Cayetano Heredia in Lima, Peru. He completed internship and residency in Internal Medicine at Advocate Illinois Masonic Medical Center in Chicago, where he served as Chief Medical Resident. Subsequently, he completed a clinical and research fellowship in Nephrology at Emory University School of Medicine. Following his training, he joined the Division of Nephrology at the Medical University of South Carolina (MUSC). After spending 11 years of intense clinical, educational and investigational efforts at MUSC, he was recruited by the Department of Nephrology at the Ochsner Clinic Foundation in 2016 to enhance the academic and clinical research programs of the department at the rank of Associate Professor of Medicine at Ochsner Clinical School / The University of Queensland (Brisbane, Australia). He serves as Clerkship Director for Medical Specialties at Ochsner Clinical School. He was appointed as Chair of Nephrology at Ochsner Health System in early 2019. Dr. Velez also holds an appointment as Adjunct Associate Professor of Physiology at Tulane University. Dr. Velez has conducted experimental research in the area of the intrarenal renin-angiotensin system (RAS) that resulted in federal funding and peer-reviewed publications. His work highlighted the role of the angiotensinase aminopeptidase A in glomerular RAS homeostasis. Currently, his areas of expertise and ongoing basic, clinical and translational investigation include hepatorenal syndrome, urinary sediment microscopy, hyponatremia, proteinuric glomerular diseases, kidney ultrasonography, renal syndromes associated with exposure to antimicrobials, and more recently, kidney disease associated with COVID-19. Dr. Velez is certified in Nephrology by the American Board of Internal Medicine, in Kidney Ultrasonography by the American Society of Diagnostic and Interventional Nephrology, and as a Hypertension Specialist by the American Society of Hypertension. He is a selected member of the SSCI. In addition, he served in the American Society of Nephrology (ASN) / National Board of Medical Examiners Fellows In-Training Examination Development Committee. He is a current member of the editorial board of Kidney360 and the ASN COVID-19 Acute Kidney Care Subcommittee.

• Befeler, Alex, Saint Louis University, Saint Louis, Missouri, United States

Alex Befeler,

• Kurtz, Ira, UCLA Medical Center, Los Angeles, California, United States

Ira Kurtz,

• Gallegos-Orozco, Juan F., University of Utah Health, Salt Lake City, Utah, United States

Juan F. Gallegos-Orozco,

• Vargas, Hugo E., Mayo Clinic, Phoenix, Arizona, United States

Hugo E. Vargas,

• Vierling, John M., Baylor College of Medicine, Houston, Texas, United States

John M. Vierling,

• Pappas, S. Chris, Orphan Therapeutics, Lebanon, New Jersey, United States

S. Chris Pappas,

• Jamil, Khurram, Mallinckrodt Pharmaceuticals Specialty Brands Principal Office, Bedminster, New Jersey, United States

Khurram Jamil,

Background

Hepatorenal syndrome type 1 (HRS-1) is an ominous form of acute kidney injury in patients with cirrhosis. Recently, the results of the randomized placebo (PBO)-controlled trial (RCT) CONFIRM demonstrated that terlipressin (TERLI) is effective in reversing HRS-1 and in reducing the cumulative need for renal replacement therapy (RRT). However, whether TERLI reduces the need for RRT among survivors has not been determined.

Methods

CONFIRM (NCT02770716) was a North American RCT (n=300) that compared HRS-1 reversal rates between patients treated with albumin plus TERLI (n=199) or albumin plus PBO (n=101) (2:1). We conducted a post hoc intention-to-treat analysis to assess the incidence of RRT among CONFIRM survivors. We also conducted a pooled analysis of the 3 TERLI RCTs in HRS-1 (OT-0401 [NCT00089570], REVERSE [NCT01143246], and CONFIRM) to examine 90-day RRT-free survival rates.

Results

In CONFIRM, the cumulative incidences of need for RRT for TERLI at day 14, 30, and 90 were 23%, 26%, and 29% compared with 35%, 36%, and 39% for patients assigned to PBO (P=0.03, 0.07, and 0.1, respectively). Among survivors, significantly fewer TERLI-treated patients remained dependent on RRT at day 14, 30, and 90 (22%, 26%, and 30%, respectively) compared with PBO (39%, 43%, and 46%; P<0.01, P=0.03, and P=0.05, respectively). The 90-day RRT-free survival rate was 35% in the TERLI group vs 30% in the PBO group (P=0.08), with a numerically longer median number of days in the TERLI group (20 vs 11). Pooled analysis of the 3 RCTs revealed a greater 90-day RRT-free survival rate for TERLI-treated (n=352) compared with PBO-treated (n=256) patients (37% vs 29%, P=0.03; OR [95% CI], 1.47 [1.04, 2.07]).

Conclusion

Treatment with TERLI added to albumin decreased the rate of RRT and improved RRT-free survival in patients with HRS-1. This is the first pharmacological intervention proven to reduce the need for RRT in patients with HRS-1. Because of the significant impact of RRT on quality of life, this observation expands the clinical benefit of TERLI and enhances the reported efficacy of TERLI in inducing HRS-1 reversal.