背景:心脏手术相关的急性肾损伤(AKI)会增加死亡率和发病率,以及慢性肾脏病的发病率,危重的幸存者。这项研究的目的是调查尿液代谢变化与心脏手术相关的AKI之间的可能联系。
方法:使用超高效液相色谱与Q-ExactiveOrbitrap质谱联用,对不同时间点心脏手术相关AKI患者组的尿液样本进行非靶向代谢组学研究,包括之前_AKI(未受伤的肾脏),AKI_Day1(受损肾)和AKI_Day14(恢复肾)组。采用多变量和单变量相结合的统计方法对三组数据进行分析,并对心脏手术后患者尿中与AKI相关的代谢产物进行筛查。通过检查京都基因百科全书和基因组数据库鉴定与心脏手术诱导的AKI相关的改变的代谢途径。
结果:使用多变量和单变量统计分析,受损肾脏分泌的尿代谢组可与未受损或康复患者的尿代谢组良好分离。然而,来自AKI_Day14和AKI之前组的尿液样本无法使用两种统计分析中的任何一种进行区分。通过生物信息学方法在注释级别1-4鉴定了近4000种尿液代谢物。这些差异代谢物中的几种也可以执行基本的生物学功能。还进行了组间尿代谢组的差异分析,以提供潜在的预后指标和信号通路的变化。与未损伤肾组相比,与心脏手术相关的AKI患者的肾脏代谢发生了戏剧性的变化,包括硫代谢和氨基酸代谢。
结论:由于局部缺血和药物治疗,心脏手术相关AKI患者出现尿代谢紊乱,康复患者的肾脏能够恢复正常。这项工作提供了有关尿液代谢物标记的数据,并为AKI的进一步研究提供了必要的资源。
BACKGROUND: Cardiac surgery-associated acute kidney injury (AKI) can increase the mortality and morbidity, and the incidence of chronic kidney disease, in critically ill survivors. The purpose of this research was to investigate possible links between urinary metabolic changes and cardiac surgery-associated AKI.
METHODS: Using ultra-high-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry, non-targeted metabolomics was performed on urinary samples collected from groups of patients with cardiac surgery-associated AKI at different time points, including Before_AKI (uninjured kidney), AKI_Day1 (injured kidney) and AKI_Day14 (recovered kidney) groups. The data among the three groups were analyzed by combining multivariate and univariate statistical methods, and urine metabolites related to AKI in patients after cardiac surgery were screened. Altered metabolic pathways associated with cardiac surgery-induced AKI were identified by examining the Kyoto Encyclopedia of Genes and Genomes database.
RESULTS: The secreted urinary metabolome of the injured kidney can be well separated from the urine metabolomes of uninjured or recovered patients using multivariate and univariate statistical analyses. However, urine samples from the AKI_Day14 and Before_AKI groups cannot be distinguished using either of the two statistical analyses. Nearly 4000 urinary metabolites were identified through bioinformatics methods at Annotation Levels 1-4. Several of these differential metabolites may also perform essential biological functions. Differential analysis of the urinary metabolome among groups was also performed to provide potential prognostic indicators and changes in signalling pathways. Compared with the uninjured kidney group, the patients with cardiac surgery-associated AKI displayed dramatic changes in renal metabolism, including sulphur metabolism and amino acid metabolism.
CONCLUSIONS: Urinary metabolite disorder was observed in patients with cardiac surgery-associated AKI due to ischaemia and medical treatment, and the recovered patients\' kidneys were able to return to normal. This work provides data on urine metabolite markers and essential resources for further research on AKI.