Defining Renal Recovery in Patients With Hepatorenal Syndrome‐Acute Kidney Injury: Experience From North American Studies

ABSTRACT Introduction The degree of improvement in serum creatinine (SCr) has previously been suggested as a sensitive indicator of treatment response in patients with hepatorenal syndrome‐acute kidney injury (HRS‐AKI), while HRS reversal remains the primary endpoint in clinical trials. Methods A to...

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Main Authors: Muhammad A. Mujtaba, Hussien Elsiesy, Sara Faiz, Syed A. Hussain, Ann Kathleen N. Gamilla‐Crudo, Aftab Karim, Mohammad Irfan Khan, Muhammad Waqar Khattak, Zunaira Zafar, Michael Kueht, Khurram Jamil
Format: Article
Language:English
Published: Wiley 2024-12-01
Series:JGH Open
Online Access:https://doi.org/10.1002/jgh3.70058
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author Muhammad A. Mujtaba
Hussien Elsiesy
Sara Faiz
Syed A. Hussain
Ann Kathleen N. Gamilla‐Crudo
Aftab Karim
Mohammad Irfan Khan
Muhammad Waqar Khattak
Zunaira Zafar
Michael Kueht
Khurram Jamil
author_facet Muhammad A. Mujtaba
Hussien Elsiesy
Sara Faiz
Syed A. Hussain
Ann Kathleen N. Gamilla‐Crudo
Aftab Karim
Mohammad Irfan Khan
Muhammad Waqar Khattak
Zunaira Zafar
Michael Kueht
Khurram Jamil
author_sort Muhammad A. Mujtaba
collection DOAJ
description ABSTRACT Introduction The degree of improvement in serum creatinine (SCr) has previously been suggested as a sensitive indicator of treatment response in patients with hepatorenal syndrome‐acute kidney injury (HRS‐AKI), while HRS reversal remains the primary endpoint in clinical trials. Methods A total of ≥ 30% SCr improvement was analyzed as an exploratory prespecified endpoint in the CONFIRM trial. In this post hoc analysis, intent‐to‐treat population data from three Phase 3 studies (OT‐0401, REVERSE, and CONFIRM) conducted in North America in patients with HRS‐AKI were pooled to assess the incidence of > 30% improvement in SCr and its association with clinical outcomes. Results Significantly more patients treated with terlipressin achieved > 30% improvement in SCr compared with those who received a placebo (42.9% vs. 23.4%; p < 0.001). Compared with patients who did not achieve > 30% improvement in SCr, those who achieved this threshold had a lower incidence of renal replacement therapy (RRT) (55.2% vs. 14%, respectively; p < 0.001) and greater overall survival at Day 90 (41.6% vs. 71.1%, respectively; p < 0.001); a greater proportion achieved durability of HRS reversal (1% [95% confidence interval, 95% CI: 0] vs. 68.9% [95% CI: 0.6, 0.8]) and more patients were alive without RRT (22.7% vs. 61.6%, respectively; p < 0.001) or transplant (11.6% vs. 43.0%, respectively; p < 0.0001). Additionally, the overall survival and RRT‐free survival in the group that achieved > 30% improvement in SCr without HRS reversal were comparable to the overall group that achieved HRS reversal. Conclusion A total of > 30% improvement in SCr levels even without HRS reversal may serve as a clinically meaningful endpoint to define renal recovery in patients with HRS‐AKI.
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spelling doaj-art-c92a7822d87f40f798bb660f2f95a2482024-12-30T04:16:37ZengWileyJGH Open2397-90702024-12-01812n/an/a10.1002/jgh3.70058Defining Renal Recovery in Patients With Hepatorenal Syndrome‐Acute Kidney Injury: Experience From North American StudiesMuhammad A. Mujtaba0Hussien Elsiesy1Sara Faiz2Syed A. Hussain3Ann Kathleen N. Gamilla‐Crudo4Aftab Karim5Mohammad Irfan Khan6Muhammad Waqar Khattak7Zunaira Zafar8Michael Kueht9Khurram Jamil10University of Texas Medical Branch Galveston Texas USATexas Christian University Fort Worth Texas USAUniversity of Texas Medical Branch Galveston Texas USAUniversity of Texas Medical Branch Galveston Texas USAUniversity of Texas Medical Branch Galveston Texas USATexas Health Presbyterian Hospital Dallas Texas USAThomas Jefferson University Hospital Philadelphia Pennsylvania USAUniversity of Illinois Peoria Peoria Illinois USASt. Mary Medical Center, Langhorne Pennsylvania USAUniversity of Texas Medical Branch Galveston Texas USAMallinckrodt Pharmaceuticals Bridgewater New Jersey USAABSTRACT Introduction The degree of improvement in serum creatinine (SCr) has previously been suggested as a sensitive indicator of treatment response in patients with hepatorenal syndrome‐acute kidney injury (HRS‐AKI), while HRS reversal remains the primary endpoint in clinical trials. Methods A total of ≥ 30% SCr improvement was analyzed as an exploratory prespecified endpoint in the CONFIRM trial. In this post hoc analysis, intent‐to‐treat population data from three Phase 3 studies (OT‐0401, REVERSE, and CONFIRM) conducted in North America in patients with HRS‐AKI were pooled to assess the incidence of > 30% improvement in SCr and its association with clinical outcomes. Results Significantly more patients treated with terlipressin achieved > 30% improvement in SCr compared with those who received a placebo (42.9% vs. 23.4%; p < 0.001). Compared with patients who did not achieve > 30% improvement in SCr, those who achieved this threshold had a lower incidence of renal replacement therapy (RRT) (55.2% vs. 14%, respectively; p < 0.001) and greater overall survival at Day 90 (41.6% vs. 71.1%, respectively; p < 0.001); a greater proportion achieved durability of HRS reversal (1% [95% confidence interval, 95% CI: 0] vs. 68.9% [95% CI: 0.6, 0.8]) and more patients were alive without RRT (22.7% vs. 61.6%, respectively; p < 0.001) or transplant (11.6% vs. 43.0%, respectively; p < 0.0001). Additionally, the overall survival and RRT‐free survival in the group that achieved > 30% improvement in SCr without HRS reversal were comparable to the overall group that achieved HRS reversal. Conclusion A total of > 30% improvement in SCr levels even without HRS reversal may serve as a clinically meaningful endpoint to define renal recovery in patients with HRS‐AKI.https://doi.org/10.1002/jgh3.70058
spellingShingle Muhammad A. Mujtaba
Hussien Elsiesy
Sara Faiz
Syed A. Hussain
Ann Kathleen N. Gamilla‐Crudo
Aftab Karim
Mohammad Irfan Khan
Muhammad Waqar Khattak
Zunaira Zafar
Michael Kueht
Khurram Jamil
Defining Renal Recovery in Patients With Hepatorenal Syndrome‐Acute Kidney Injury: Experience From North American Studies
JGH Open
title Defining Renal Recovery in Patients With Hepatorenal Syndrome‐Acute Kidney Injury: Experience From North American Studies
title_full Defining Renal Recovery in Patients With Hepatorenal Syndrome‐Acute Kidney Injury: Experience From North American Studies
title_fullStr Defining Renal Recovery in Patients With Hepatorenal Syndrome‐Acute Kidney Injury: Experience From North American Studies
title_full_unstemmed Defining Renal Recovery in Patients With Hepatorenal Syndrome‐Acute Kidney Injury: Experience From North American Studies
title_short Defining Renal Recovery in Patients With Hepatorenal Syndrome‐Acute Kidney Injury: Experience From North American Studies
title_sort defining renal recovery in patients with hepatorenal syndrome acute kidney injury experience from north american studies
url https://doi.org/10.1002/jgh3.70058
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