Urinary 3-methylhistidine as a potential biomarker for sepsis-associated acute kidney injury: multidimensional metabolomics analysis in mice and human.

Background: Sepsis-associated acute kidney injury (SA-AKI) is strongly associated with increased mortality in critical patients. The early detection of SA-AKI is crucial for clinical intervention. This study aims to integrate multiple metabolomics data related to SA-AKI to identify and validate nove...

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Publicado en:Annals of Intensive Care Vol. 15; no. 1; pp. 1 - 18
Autores principales: Wang, Xibo, Huang, Pengfei, Luo, Yinghao, Xin, Yu, Li, Yue, Shen, Lifeng, Liu, Yanqi, Zhou, Yang, Zhang, Yuxin, Zhang, Qianqian, Wang, Dawei, Luan, Feiyu, Zhang, Weiting, Yuan, Mengyao, Liu, Yuhan, Liu, Fengye, Zhang, Nan, Wu, Jinyuan, Wu, Tao, Wang, Xuan
Formato: Journal Article
Publicado: Elsevier B.V. 8/26/2025
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 8/26/2025
      vid: 15
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      pub: Elsevier B.V.
      place: New York, New York
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        187773853
        10.1186/s13613-025-01550-z
        187773853
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        atl: Urinary 3-methylhistidine as a potential biomarker for sepsis-associated acute kidney injury: multidimensional metabolomics analysis in mice and human.
      aug:
        au:
          Wang, Xibo
          Huang, Pengfei
          Luo, Yinghao
          Xin, Yu
          Li, Yue
          Shen, Lifeng
          Liu, Yanqi
          Zhou, Yang
          Zhang, Yuxin
          Zhang, Qianqian
          Wang, Dawei
          Luan, Feiyu
          Zhang, Weiting
          Yuan, Mengyao
          Liu, Yuhan
          Liu, Fengye
          Zhang, Nan
          Wu, Jinyuan
          Wu, Tao
          Wang, Xuan
        affil: https://ror.org/05vy2sc54 Departments of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin Medical University, 150001, Harbin, Heilongjiang, China
      sug:
      ab: Background: Sepsis-associated acute kidney injury (SA-AKI) is strongly associated with increased mortality in critical patients. The early detection of SA-AKI is crucial for clinical intervention. This study aims to integrate multiple metabolomics data related to SA-AKI to identify and validate novel metabolic markers. Methods: Real-time glomerular filtration rate (RT-GFR) measurement was adopted to establish SA-AKI mice. Untargeted metabolomics sequencing was performed on SA-AKI mice renal tissue (Control—LPS-8 h—LPS-24 h, N = 4) and urine samples (Control group vs. LPS-24 h group, N = 6). Time series analysis and random forest algorithm were employed to identify key metabolic molecule. Subsequently, renal spatiotemporal metabolomics was used to explore the specific distribution of key molecule. Eventually, a clinical cohort (20 healthy volunteers vs. 30 sepsis patients vs. 45 SA-AKI patients) urine quantitative metabolomic analysis was carried out to validate it as a biomarker and construct a diagnostic model via logistic regression (LR). Results: Forty-two key renal metabolites and top fifty urinary metabolites were determined through multidimensional metabolomics study of SA-AKI mice. Urinary 3-Methylhistidine (3-MH) was charactered as a potential biomarker. The distribution of 3-MH increased in collecting ducts through renal spatiotemporal metabolomics sequencing. Then, we recruited 95 urine samples to validate its diagnostic performance (AUC = 0.86, 95% CI 0.77–0.95) and its role as an independent predictive factor for SA-AKI (OR = 0.21, 95% CI: 0.05–0.84, p < 0.05). Ultimately, a diagnostic model combined urinary 3-MH with clinical variables was constructed to identify SA-AKI (AUC = 0.89, 95% CI 0.74–1.00). Conclusions: We proposed that urinary 3-Methylhistidine has potential diagnostic value for SA-AKI screening. Future studies will focus on its performance in other clinical populations to comprehensively evaluate its diagnostic role.
      pubtype: Academic Journal
      doctype: Journal Article
      ougenre: Article
    language: English
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