Gender Affects the Association Between Serum Creatinine Levels and Clinical Response to Terlipressin in Patients with Hepatorenal Syndrome Type of Acute Kidney Injury
1Hepatology, Mallinckrodt Pharmaceuticals, Clinton, NJ, 2Liver Disease/Hepatology & Transplant Hepatology, California Pacific Medical Center, San Francisco, CA, 3Orphan Therapeutics, LLC, Longboat Key, FL
Meeting: 2022 American Transplant Congress
Abstract number: 122
Keywords: Liver, Liver cirrhosis
Topic: Clinical Science » Liver » 53 - Liver: Cirrhosis - Portal Hypertension and Other Complications
Session Information
Session Name: Cirrhosis: Complications, Portal Hypertension and Renal Management
Session Type: Rapid Fire Oral Abstract
Date: Sunday, June 5, 2022
Session Time: 5:30pm-7:00pm
Presentation Time: 5:30pm-5:40pm
Location: Hynes Room 311
*Purpose: Hepatorenal syndrome (HRS)-acute kidney injury (AKI) is a rare and serious complication of cirrhosis, with serum creatinine (SCr) used diagnostically. Women generally have less muscle mass and consequently lower SCr levels than men with similar renal function. Terlipressin more effectively reverses HRS when started at lower SCr levels. The largest randomized, prospective database of placebo-controlled studies in patients (pts) with HRS-AKI was examined to assess a gender-based impact on treatment response.
*Methods: Pooled data from 3 phase III US studies (OT-0401, REVERSE, CONFIRM) were used; pts with HRS-AKI were treated with terlipressin plus albumin (terli) or placebo plus albumin (pbo). Associations between baseline (BL) SCr (SCr upon treatment initiation) and clinical response (complete response [CR]: HRS reversal, SCr [1.5 or less] or partial response [PR]: at least 30% improvement in SCr) stratified by treatment and gender were assessed. Overall response rate (ORR) comprised pts with a CR or PR; P values were calculated using a Fisher’s exact test.
*Results: Males in the terli group with BL SCr <3 had significant improvements in CR and ORR, relative to pbo, while females did not (Table). Among pts with a BL SCr of 3-5, both males and females had a significant improvement in ORR (terli vs pbo); however, only males had significant improvements in CR. Across genders, ≤5 pts with a BL SCr >5 demonstrated a response to treatment (P>.05 vs pbo).
*Conclusions: Pts in the terli group had a greater clinical response vs pbo for BL SCr of <5. Males were more likely to have a CR and ORR than females, especially those with BL SCr 3-5. Despite matched SCr, females had a lower response than males, likely reflecting more advanced renal dysfunction upon treatment initiation. New guidance recommending initiation of vasoconstrictor treatment based on SCr change from BL rather than absolute cut-offs may improve outcomes for female pts. Additional biomarkers to evaluate renal dysfunction should also be evaluated.
| BL SCr <3 | BL SCr 3-5 | |||||
| Parameter, n (%) | Terli | Pbo | P value | Terli | Pbo | P value |
| Male | 74 | 47 | 112 | 96 | ||
| HRS Reversal | 36 (48.6) | 13 (27.7) | .024 | 35 (31.3) | 11 (11.5) | <.001 |
| ORR | 42 (56.8) | 15 (31.9) | .009 | 54 (48.2) | 24 (25.0) | <.001 |
| Female | 52 | 37 | 71 | 46 | ||
| HRS Reversal | 26 (50.0) | 12 (32.4) | .129 | 16 (22.5) | 5 (10.9) | .141 |
| ORR | 27 (51.9) | 13 (35.1) | .135 | 24 (33.8) | 6 (13.0) | .016 |
To cite this abstract in AMA style:
Jamil K, Frederick R, Pappas S. Gender Affects the Association Between Serum Creatinine Levels and Clinical Response to Terlipressin in Patients with Hepatorenal Syndrome Type of Acute Kidney Injury [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/gender-affects-the-association-between-serum-creatinine-levels-and-clinical-response-to-terlipressin-in-patients-with-hepatorenal-syndrome-type-of-acute-kidney-injury/. Accessed May 30, 2025.« Back to 2022 American Transplant Congress