Ammonia and urea metabolism in acute liver failure: A multicentre cohort study

IF 6 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Liver International Pub Date : 2024-07-17 DOI:10.1111/liv.16043

Filipe S. Cardoso, David Toapanta, Natalia Jimenez, Pedro Fidalgo, António Figueiredo, Miriam Valdivieso, Nuno Germano, Jody A. Rule, William M. Lee, Juan G. Abraldes, Enric Reverter, Constantine J. Karvellas

{"title":"Ammonia and urea metabolism in acute liver failure: A multicentre cohort study","authors":"Filipe S. Cardoso, David Toapanta, Natalia Jimenez, Pedro Fidalgo, António Figueiredo, Miriam Valdivieso, Nuno Germano, Jody A. Rule, William M. Lee, Juan G. Abraldes, Enric Reverter, Constantine J. Karvellas","doi":"10.1111/liv.16043","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background & Aims</h3>\n \n <p>Ammonia is metabolized into urea in the liver. In acute liver failure (ALF), ammonia has been associated with survival. However, urea variation has been poorly studied.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Observational cohort including ALF patients from Curry Cabral Hospital (Lisbon, Portugal) and Clinic Hospital (Barcelona, Spain) between 10/2010 and 01/2023. The United States ALF Study Group cohort was used for external validation. Primary exposures were serum ammonia and urea on ICU admission. Primary endpoint was 30-day transplant-free survival (TFS). Secondary endpoint was explanted liver weight.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Among 191 ALF patients, median (IQR) age was 46 (32; 57) years and 85 (44.5%) were males. Overall, 86 (45.0%) patients were transplanted and 75 (39.3%) died. Among all ALF patients, following adjustment for age, sex, body weight, and aetiology, higher ammonia or lower urea was independently associated with higher INR on ICU admission (<i>p</i> < .009). Among all ALF patients, following adjustment for sex, aetiology, and lactate, higher ammonia was independently associated with lower TFS (adjusted odds ratio (95% confidence interval [CI]) = 0.991 (0.985; 0.997); <i>p</i> = .004). This model predicted TFS with good discrimination (area under receiver operating curve [95% CI] = 0.78 [0.75; 0.82]) and reasonable calibration (<i>R</i><sup>2</sup> of 0.43 and Brier score of 0.20) after external validation. Among transplanted patients, following adjustment for age, sex, actual body weight, and aetiology, higher ammonia (<i>p</i> = .024) or lower (<i>p</i> < .001) urea was independently associated with lower explanted liver weight.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Among ALF patients, serum ammonia and urea were associated with ALF severity. A score incorporating serum ammonia predicted TFS reasonably well.</p>\n </section>\n </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0000,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Liver International","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/liv.16043","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background & Aims

Ammonia is metabolized into urea in the liver. In acute liver failure (ALF), ammonia has been associated with survival. However, urea variation has been poorly studied.

Methods

Observational cohort including ALF patients from Curry Cabral Hospital (Lisbon, Portugal) and Clinic Hospital (Barcelona, Spain) between 10/2010 and 01/2023. The United States ALF Study Group cohort was used for external validation. Primary exposures were serum ammonia and urea on ICU admission. Primary endpoint was 30-day transplant-free survival (TFS). Secondary endpoint was explanted liver weight.

Results

Among 191 ALF patients, median (IQR) age was 46 (32; 57) years and 85 (44.5%) were males. Overall, 86 (45.0%) patients were transplanted and 75 (39.3%) died. Among all ALF patients, following adjustment for age, sex, body weight, and aetiology, higher ammonia or lower urea was independently associated with higher INR on ICU admission (p < .009). Among all ALF patients, following adjustment for sex, aetiology, and lactate, higher ammonia was independently associated with lower TFS (adjusted odds ratio (95% confidence interval [CI]) = 0.991 (0.985; 0.997); p = .004). This model predicted TFS with good discrimination (area under receiver operating curve [95% CI] = 0.78 [0.75; 0.82]) and reasonable calibration (R² of 0.43 and Brier score of 0.20) after external validation. Among transplanted patients, following adjustment for age, sex, actual body weight, and aetiology, higher ammonia (p = .024) or lower (p < .001) urea was independently associated with lower explanted liver weight.

Conclusions

Among ALF patients, serum ammonia and urea were associated with ALF severity. A score incorporating serum ammonia predicted TFS reasonably well.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

急性肝衰竭的氨和尿素代谢：一项多中心队列研究。

背景与目的：氨在肝脏中代谢为尿素。在急性肝衰竭（ALF）中，氨与存活率有关。然而，对尿素变化的研究却很少：观察队列包括 2010 年 10 月至 2023 年 1 月期间来自 Curry Cabral 医院（葡萄牙里斯本）和 Clinic 医院（西班牙巴塞罗那）的 ALF 患者。美国 ALF 研究组队列用于外部验证。主要暴露指标为ICU入院时的血清氨和尿素。主要终点是30天无移植生存率（TFS）。次要终点是切除肝脏的重量：在191名ALF患者中，中位（IQR）年龄为46（32；57）岁，85（44.5%）人为男性。总体而言，86（45.0%）名患者接受了移植，75（39.3%）名患者死亡。在所有 ALF 患者中，在对年龄、性别、体重和病因进行调整后，经外部验证，较高的氨或较低的尿素与较高的入院 INR 独立相关（p 2 为 0.43，Brier 评分为 0.20）。在移植患者中，在对年龄、性别、实际体重和病因进行调整后，较高的氨（P = 0.024）或较低的尿素（P = 0.024）与较高的INR（P = 0.024）或较低的INR（P = 0.024）有独立的相关性：在 ALF 患者中，血清氨和尿素与 ALF 严重程度相关。结合血清氨的评分能较好地预测 TFS。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Liver International 医学-胃肠肝病学

CiteScore

13.90

自引率

4.50%

发文量

348

审稿时长

2 months

期刊介绍： Liver International promotes all aspects of the science of hepatology from basic research to applied clinical studies. Providing an international forum for the publication of high-quality original research in hepatology, it is an essential resource for everyone working on normal and abnormal structure and function in the liver and its constituent cells, including clinicians and basic scientists involved in the multi-disciplinary field of hepatology. The journal welcomes articles from all fields of hepatology, which may be published as original articles, brief definitive reports, reviews, mini-reviews, images in hepatology and letters to the Editor.