Metabolomics- and proteomics-based multi-omics integration reveals early metabolite alterations in sepsis-associated acute kidney injury

作者：Pengfei Huang, Yanqi Liu, Yue Li, Xin Yu, Chuanchuan Nan, Yinghao Luo, Yating Feng, Nana Jin, Yahui Peng, Dawei Wang, Yang Zhou, Feiyu Luan, Xinran Wang, Xibo Wang, Hongxu Li, Yuxin Zhou, Weiting Zhang, Yuhan Liu, Mengyao Yuan, Yuxin Zhang, Yu‐Chen Song, Xiao Yu, Lifeng Shen, Kaijiang Yu, Mingyan Zhao, Lixin Cheng, Changsong Wang · 发表于：BMC Medicine · 年份：2025 · DOI：10.1186/s12916-025-03920-7 · 被引用次数：38 · 研究领域：Metabolomics and Mass Spectrometry Studies、Acute Kidney Injury Research、Sepsis Diagnosis and Treatment

BACKGROUND: Sepsis-associated acute kidney injury (SA-AKI) is a frequent complication in patients with sepsis and is associated with high mortality. Therefore, early recognition of SA-AKI is essential for administering supportive treatment and preventing further damage. This study aimed to identify and validate metabolite biomarkers of SA-AKI to assist in early clinical diagnosis. METHODS: Untargeted renal proteomic and metabolomic analyses were performed on the renal tissues of LPS-induced SA-AKI and sepsis mice. Glomerular filtration rate (GFR) monitoring technology was used to evaluate real-time renal function in mice. To elucidate the distinctive characteristics of SA-AKI, a multi-omics Spearman correlation network was constructed integrating core metabolites, proteins, and renal function. Subsequently, metabolomics analysis was used to explore the dynamic changes of core metabolites in the serum of SA-AKI mice at 0, 8, and 24 h. Finally, a clinical cohort (28 patients with SA-AKI vs. 28 patients with sepsis) serum quantitative metabolomic analysis was carried out to build a diagnostic model for SA-AKI via logistic regression (LR). RESULTS: Thirteen differential renal metabolites and 112 differential renal proteins were identified through a multi-omics study of SA-AKI mice. Subsequently, a multi-omics correlation network was constructed to highlight five core metabolites, i.e., 3-hydroxybutyric acid, 3-hydroxymethylglutaric acid, creatine, myristic acid, and inosine, the ...