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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Published in:JGH open 2024-12, Vol.8 (12), p.e70058-n/a
Main Authors: Mujtaba, Muhammad A., Elsiesy, Hussien, Faiz, Sara, Hussain, Syed A., Gamilla‐Crudo, Ann Kathleen N., Karim, Aftab, Khan, Mohammad Irfan, Khattak, Muhammad Waqar, Zafar, Zunaira, Kueht, Michael, Jamil, Khurram
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Demographics
Kidneys
Liver cirrhosis
Medical prognosis
Original
Population
Transplants & implants
Variance analysis
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creator Mujtaba, Muhammad A.
Elsiesy, Hussien
Faiz, Sara
Hussain, Syed A.
Gamilla‐Crudo, Ann Kathleen N.
Karim, Aftab
Khan, Mohammad Irfan
Khattak, Muhammad Waqar
Zafar, Zunaira
Kueht, Michael
Jamil, Khurram
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  30% improvement in SCr, those who achieved this threshold had a lower incidence of renal replacement therapy (RRT) (55.2% vs. 14%, respectively; p 
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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 &gt; 30% improvement in SCr and its association with clinical outcomes. Results Significantly more patients treated with terlipressin achieved &gt; 30% improvement in SCr compared with those who received a placebo (42.9% vs. 23.4%; p &lt; 0.001). Compared with patients who did not achieve &gt; 30% improvement in SCr, those who achieved this threshold had a lower incidence of renal replacement therapy (RRT) (55.2% vs. 14%, respectively; p &lt; 0.001) and greater overall survival at Day 90 (41.6% vs. 71.1%, respectively; p &lt; 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 &lt; 0.001) or transplant (11.6% vs. 43.0%, respectively; p &lt; 0.0001). Additionally, the overall survival and RRT‐free survival in the group that achieved &gt; 30% improvement in SCr without HRS reversal were comparable to the overall group that achieved HRS reversal. Conclusion A total of &gt; 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.</description><identifier>ISSN: 2397-9070</identifier><identifier>EISSN: 2397-9070</identifier><identifier>DOI: 10.1002/jgh3.70058</identifier><identifier>PMID: 39664961</identifier><language>eng</language><publisher>Melbourne: Wiley Publishing Asia Pty Ltd</publisher><subject>Demographics ; Kidneys ; Liver cirrhosis ; Medical prognosis ; Original ; Population ; Transplants &amp; implants ; Variance analysis</subject><ispartof>JGH open, 2024-12, Vol.8 (12), p.e70058-n/a</ispartof><rights>2024 The Author(s). published by Journal of Gastroenterology and Hepatology Foundation and John Wiley &amp; Sons Australia, Ltd.</rights><rights>2024 The Author(s). JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley &amp; Sons Australia, Ltd.</rights><rights>2024. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c4048-d313b6f46a7bb9ef22e23bd6781bbd205e8d21013238b2a9e9fac05fdee1da133</cites><orcidid>0000-0001-9155-3513</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/3149931137/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/3149931137?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,11561,25752,27923,27924,37011,37012,44589,46051,46475,53790,53792,74897</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39664961$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mujtaba, Muhammad A.</creatorcontrib><creatorcontrib>Elsiesy, Hussien</creatorcontrib><creatorcontrib>Faiz, Sara</creatorcontrib><creatorcontrib>Hussain, Syed A.</creatorcontrib><creatorcontrib>Gamilla‐Crudo, Ann Kathleen N.</creatorcontrib><creatorcontrib>Karim, Aftab</creatorcontrib><creatorcontrib>Khan, Mohammad Irfan</creatorcontrib><creatorcontrib>Khattak, Muhammad Waqar</creatorcontrib><creatorcontrib>Zafar, Zunaira</creatorcontrib><creatorcontrib>Kueht, Michael</creatorcontrib><creatorcontrib>Jamil, Khurram</creatorcontrib><title>Defining Renal Recovery in Patients With Hepatorenal Syndrome‐Acute Kidney Injury: Experience From North American Studies</title><title>JGH open</title><addtitle>JGH Open</addtitle><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 &gt; 30% improvement in SCr and its association with clinical outcomes. Results Significantly more patients treated with terlipressin achieved &gt; 30% improvement in SCr compared with those who received a placebo (42.9% vs. 23.4%; p &lt; 0.001). Compared with patients who did not achieve &gt; 30% improvement in SCr, those who achieved this threshold had a lower incidence of renal replacement therapy (RRT) (55.2% vs. 14%, respectively; p &lt; 0.001) and greater overall survival at Day 90 (41.6% vs. 71.1%, respectively; p &lt; 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 &lt; 0.001) or transplant (11.6% vs. 43.0%, respectively; p &lt; 0.0001). Additionally, the overall survival and RRT‐free survival in the group that achieved &gt; 30% improvement in SCr without HRS reversal were comparable to the overall group that achieved HRS reversal. 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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 &gt; 30% improvement in SCr and its association with clinical outcomes. Results Significantly more patients treated with terlipressin achieved &gt; 30% improvement in SCr compared with those who received a placebo (42.9% vs. 23.4%; p &lt; 0.001). Compared with patients who did not achieve &gt; 30% improvement in SCr, those who achieved this threshold had a lower incidence of renal replacement therapy (RRT) (55.2% vs. 14%, respectively; p &lt; 0.001) and greater overall survival at Day 90 (41.6% vs. 71.1%, respectively; p &lt; 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 &lt; 0.001) or transplant (11.6% vs. 43.0%, respectively; p &lt; 0.0001). Additionally, the overall survival and RRT‐free survival in the group that achieved &gt; 30% improvement in SCr without HRS reversal were comparable to the overall group that achieved HRS reversal. Conclusion A total of &gt; 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.</abstract><cop>Melbourne</cop><pub>Wiley Publishing Asia Pty Ltd</pub><pmid>39664961</pmid><doi>10.1002/jgh3.70058</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-9155-3513</orcidid><oa>free_for_read</oa></addata></record>
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subjects Demographics
Kidneys
Liver cirrhosis
Medical prognosis
Original
Population
Transplants & implants
Variance analysis
title Defining Renal Recovery in Patients With Hepatorenal Syndrome‐Acute Kidney Injury: Experience From North American Studies
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