Hong Hao, Zhou Suya, Zheng Junyao, Shi Haimin, Chen Yue, Li Ming
Department of Intensive Care Unit, The First Affiliated Hospital of Soochow University, Soochow, Suzhou, People's Republic of China.
Laboratory Nephrology, Jinshan hospital of Fudan University, Shanghai, People's Republic of China.
J Inflamm Res. 2024 Aug 17;17:5521-5531. doi: 10.2147/JIR.S461621. eCollection 2024.
The aim of this study was to investigate the changes of different metabolites in the body fluids of non-dialysis patients with chronic kidney disease (CKD) using a metabolomics approach. The goal was to identify early biomarkers of CKD progression through metabolic pathway analysis.
Plasma samples from 47 patients with stages 1-4 CKD not requiring dialysis and 30 healthy controls were analyzed by liquid chromatography-mass spectrometry (LC-MS). Using multivariate data analysis, specifically a partially orthogonal least squares discriminant analysis model (OPLS-DA), we investigated metabolic differences between different stages of CKD. The sensitivity and specificity of the analysis were evaluated using the Area Under Curve (AUC) method. Furthermore, the metabolic pathways were analyzed using the Met PA database.
Plasma samples from CKD patients and controls were successfully differentiated using an OPLS-DA model. Initially, twenty-five compounds were identified as potential plasma metabolic markers for distinguishing CKD patients from healthy controls. Among these, six compounds (ADMA, D-Ornithine, Kynurenine, Kynurenic acid, 5-Hydroxyindoleacetic acid, and Gluconic acid) were found to be associated with CKD progression It has been found to be associated with the progression of CKD. Changes in metabolic pathways associated with CKD progression include arginine and ornithine metabolism, tryptophan metabolism, and the pentose phosphate pathway.
By analyzing the metabolic pathways of different metabolites, we have identified the significant impact of CKD progression. The main metabolic pathways involved are Arginine and Ornithine metabolism, Tryptophan metabolism, and Pentose phosphate pathway. ADMA, D-Ornithine, L-Kynurenine, Kynurenic acid, 5-Hydroxyindoleacetic acid, and Gluconic acid could serve as potential early biomarkers for CKD progression. These findings have important implications for the early intervention and treatment of CKD, as well as for further research into the underlying mechanisms of its pathogenesis.
本研究旨在采用代谢组学方法研究非透析慢性肾脏病(CKD)患者体液中不同代谢物的变化。目标是通过代谢途径分析确定CKD进展的早期生物标志物。
对47例1 - 4期无需透析的CKD患者和30例健康对照的血浆样本进行液相色谱 - 质谱(LC - MS)分析。使用多变量数据分析,特别是偏最小二乘判别分析模型(OPLS - DA),研究CKD不同阶段之间的代谢差异。采用曲线下面积(AUC)法评估分析的敏感性和特异性。此外,使用Met PA数据库分析代谢途径。
使用OPLS - DA模型成功区分了CKD患者和对照的血浆样本。最初,25种化合物被确定为区分CKD患者与健康对照的潜在血浆代谢标志物。其中,六种化合物(不对称二甲基精氨酸、D - 鸟氨酸、犬尿氨酸、犬尿酸、5 - 羟吲哚乙酸和葡萄糖酸)被发现与CKD进展相关。已发现与CKD进展相关的代谢途径变化包括精氨酸和鸟氨酸代谢、色氨酸代谢以及磷酸戊糖途径。
通过分析不同代谢物的代谢途径,我们确定了CKD进展的显著影响。主要涉及的代谢途径是精氨酸和鸟氨酸代谢、色氨酸代谢以及磷酸戊糖途径。不对称二甲基精氨酸、D - 鸟氨酸、L - 犬尿氨酸、犬尿酸、5 - 羟吲哚乙酸和葡萄糖酸可作为CKD进展的潜在早期生物标志物。这些发现对CKD的早期干预和治疗以及对其发病机制潜在机制的进一步研究具有重要意义。