A Metabolomics Approach to Identify Metabolites Associated with Uremic Symptoms in Patients Receiving Maintenance Hemodialysis.

IF 3 Q1 UROLOGY & NEPHROLOGY
Kidney360 Pub Date : 2025-09-23 DOI:10.34067/KID.0000000838
Solaf Al Awadhi, Leslie Myint, Eliseo Guallar, Clary B Clish, Kendra E Wulczyn, Sahir Kalim, Ravi Thandhani, Dorry L Segev, Mara McAdams-DeMarco, Sharon M Moe, Ranjani N Moorthi, Jonathan Himmelfarb, Neil R Powe, Marcello Tonelli, Eugene P Rhee, Tariq Shafi
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引用次数: 0

Abstract

Background: The specific toxins causing uremic symptoms (nausea, vomiting, pruritus, fatigue, difficulty concentrating and pain) in kidney failure remain unknown. We used untargeted metabolomics to identify plasma metabolites associated with uremic symptoms in patients receiving hemodialysis.

Methods: We measured metabolites in plasma samples from Longitudinal US/Canada Incident Dialysis (LUCID) study participants at baseline (discovery; n=636) and year 1 (internal validation; n=260), and from Frailty Assessment in Renal Disease (FAIR) study participants (external validation; n=355). We used metabolite-wise linear models with empirical Bayesian inference to evaluate the association between metabolites and uremic symptoms' severity, adjusting for key covariates. We accounted for multiple testing using a false discovery rate (pFDR) for linear models and used two machine learning models to evaluate the association consistency. We defined association as significant if pFDR <0.1 and consistent if they had medium or high importance in both machine learning models.

Results: Participants had a mean age of 63 years, with uremic symptom prevalence ranging from 44-83%. We identified 627 previously characterized (known) and 35,558 unknown metabolite peaks. No known metabolites were significantly and consistently associated with uremic symptoms' severity across all cohorts. Within cohorts, retinol was negatively associated with nausea/vomiting in LUCID at year 1, and indole-3-propionic acid was negatively associated with anorexia in FAIR. Several unknown metabolites were associated with symptoms (lowest pFDR, 0.0004), but none were consistent across cohorts.

Conclusions: We identified metabolites associated with uremic symptom severity, though findings were inconsistent across cohorts. This study highlights the need for further research on uremic toxins and clinical outcomes.

代谢组学方法鉴定维持性血液透析患者尿毒症症状相关代谢物
背景:引起肾衰竭患者尿毒症症状(恶心、呕吐、瘙痒、疲劳、注意力难以集中和疼痛)的特定毒素尚不清楚。我们使用非靶向代谢组学来鉴定与接受血液透析的患者尿毒症症状相关的血浆代谢物。方法:我们测量了美国/加拿大纵向透析(LUCID)研究参与者在基线(发现,n=636)和第一年(内部验证,n=260)以及肾脏疾病虚弱评估(FAIR)研究参与者(外部验证,n=355)血浆样本中的代谢产物。我们使用代谢物线性模型和经验贝叶斯推断来评估代谢物与尿毒症症状严重程度之间的关系,并对关键协变量进行调整。我们使用线性模型的错误发现率(pFDR)进行了多次测试,并使用两个机器学习模型来评估关联一致性。如果pFDR结果:参与者平均年龄为63岁,尿毒症患病率在44-83%之间,我们将关联定义为显著。我们鉴定了627个已知的代谢峰和35,558个未知的代谢峰。在所有队列中,没有已知的代谢物与尿毒症症状的严重程度显著且一致地相关。在队列中,视黄醇与LUCID患者第1年的恶心/呕吐呈负相关,吲哚-3-丙酸与FAIR患者的厌食症呈负相关。一些未知的代谢物与症状相关(最低pFDR, 0.0004),但在各队列中都不一致。结论:我们确定了与尿毒症症状严重程度相关的代谢物,尽管研究结果在各队列中不一致。这项研究强调了进一步研究尿毒症毒素和临床结果的必要性。
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来源期刊
Kidney360
Kidney360 UROLOGY & NEPHROLOGY-
CiteScore
3.90
自引率
0.00%
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0
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