{"title":"Increased circulatory Krebs cycle metabolites in sepsis is associated with increased interleukin-6 release and worse survival.","authors":"Kuei-Pin Chung, Yi-Hsuan Chen, Yi-Jung Chen, Jung-Yien Chien, Han-Chun Kuo, Yen-Tsung Huang, Sheng-Yuan Ruan, Yu-Li Lin, Yen-Fu Chen, Li-Ta Keng, Lu-Cheng Kuo, Shih-Chi Ku, Ching-Hua Kuo, Chong-Jen Yu","doi":"10.1097/SHK.0000000000002550","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Recent studies have proposed that Krebs cycle metabolites may serve as potential biomarkers for prognosis in sepsis. However, whether these metabolites are associated with disease severity and can be applied to improve the effectiveness of current prognosis assessment in sepsis remains unclear and is explored in this study.</p><p><strong>Methods: </strong>This prospective multicenter cohort study was conducted in medical intensive care units (ICUs). From December 2019 to September 2022, consecutive patients admitted to medical ICUs for sepsis were screened and recruited. Plasma samples were obtained for measurements of cytokines and Krebs cycle metabolites, including citrate/isocitrate, cis-aconitate, alpha-ketoglutarate, succinate, fumarate and malate.</p><p><strong>Results: </strong>In total, 97 patients admitted for sepsis were enrolled in the study. The 28-day mortality rate was 17.5%, and non-survivors exhibited significantly increased plasma lactate levels and Sequential Organ Failure Assessment (SOFA) scores. Plasma levels of Krebs cycle metabolites were significantly correlated with both plasma lactate and interleukin-6 levels. Except for citrate/isocitrate, all Krebs cycle metabolites were significantly elevated in patients with acute kidney injury. Multivariate Cox proportional hazard models, adjusted for plasma lactate levels and SOFA scores, revealed that plasma levels of alpha-ketoglutarate (adjusted hazard ratio [HR]: 2.404, P = 0.002), fumarate (adjusted HR: 1.904, P = 0.001) and malate (adjusted HR: 1.327, P = 0.019) were associated with increased risk of 28-day mortality.</p><p><strong>Conclusions: </strong>Study findings indicate that Krebs cycle metabolites, particularly alpha-ketoglutarate, fumarate, and malate, when applied with SOFA score, might enhance prognostic assessment in patients with sepsis.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7000,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"SHOCK","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/SHK.0000000000002550","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CRITICAL CARE MEDICINE","Score":null,"Total":0}
引用次数: 0
Abstract
Objective: Recent studies have proposed that Krebs cycle metabolites may serve as potential biomarkers for prognosis in sepsis. However, whether these metabolites are associated with disease severity and can be applied to improve the effectiveness of current prognosis assessment in sepsis remains unclear and is explored in this study.
Methods: This prospective multicenter cohort study was conducted in medical intensive care units (ICUs). From December 2019 to September 2022, consecutive patients admitted to medical ICUs for sepsis were screened and recruited. Plasma samples were obtained for measurements of cytokines and Krebs cycle metabolites, including citrate/isocitrate, cis-aconitate, alpha-ketoglutarate, succinate, fumarate and malate.
Results: In total, 97 patients admitted for sepsis were enrolled in the study. The 28-day mortality rate was 17.5%, and non-survivors exhibited significantly increased plasma lactate levels and Sequential Organ Failure Assessment (SOFA) scores. Plasma levels of Krebs cycle metabolites were significantly correlated with both plasma lactate and interleukin-6 levels. Except for citrate/isocitrate, all Krebs cycle metabolites were significantly elevated in patients with acute kidney injury. Multivariate Cox proportional hazard models, adjusted for plasma lactate levels and SOFA scores, revealed that plasma levels of alpha-ketoglutarate (adjusted hazard ratio [HR]: 2.404, P = 0.002), fumarate (adjusted HR: 1.904, P = 0.001) and malate (adjusted HR: 1.327, P = 0.019) were associated with increased risk of 28-day mortality.
Conclusions: Study findings indicate that Krebs cycle metabolites, particularly alpha-ketoglutarate, fumarate, and malate, when applied with SOFA score, might enhance prognostic assessment in patients with sepsis.
期刊介绍：
SHOCK®: Injury, Inflammation, and Sepsis: Laboratory and Clinical Approaches includes studies of novel therapeutic approaches, such as immunomodulation, gene therapy, nutrition, and others. The mission of the Journal is to foster and promote multidisciplinary studies, both experimental and clinical in nature, that critically examine the etiology, mechanisms and novel therapeutics of shock-related pathophysiological conditions. Its purpose is to excel as a vehicle for timely publication in the areas of basic and clinical studies of shock, trauma, sepsis, inflammation, ischemia, and related pathobiological states, with particular emphasis on the biologic mechanisms that determine the response to such injury. Making such information available will ultimately facilitate improved care of the traumatized or septic individual.
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