Peris-Fernández María, Roca-Marugán Marta, Amengual Julià L, Balaguer-Timor Ángel, Viejo-Boyano Iris, Soldevila-Orient Amparo, Devesa-Such Ramon, Sánchez-Pérez Pilar, Hernández-Jaras Julio
Health Research Institute Hospital La Fe, 46026 Valencia, Spain.
University and Polytechnic La Fe Hospital, 46026 Valencia, Spain.
Biomedicines. 2024 Mar 7;12(3):607. doi: 10.3390/biomedicines12030607.
Chronic kidney disease (CKD) affects approximately 12% of the global population, posing a significant health threat. Inflammation plays a crucial role in the uremic phenotype of non-dialysis-dependent (NDD) stage 5 CKD, contributing to elevated cardiovascular and overall mortality in affected individuals. This study aimed to explore novel metabolic pathways in this population using semi-targeted metabolomics, which allowed us to quantify numerous metabolites with known identities before data acquisition through an in-house polar compound library. In a prospective observational design with 50 patients, blood samples collected before the initial hemodialysis session underwent liquid chromatography and high-resolution mass spectrometer analysis. Univariate (Mann-Whitney test) and multivariate (logistic regression with LASSO regularization) methods identified metabolomic variables associated with inflammation. Notably, adenosine-5'-phosphosulfate (APS), dimethylglycine, pyruvate, lactate, and 2-ketobutyric acid exhibited significant differences in the presence of inflammation. Cholic acid, homogentisic acid, and 2-phenylpropionic acid displayed opposing patterns. Multivariate analysis indicated increased inflammation risk with certain metabolites (-Butyrylglycine, dimethylglycine, 2-Oxoisopentanoic acid, and pyruvate), while others (homogentisic acid, 2-Phenylpropionic acid, and 2-Methylglutaric acid) suggested decreased probability. These findings unveil potential inflammation-associated biomarkers related to defective mitochondrial fatty acid beta oxidation and branched-chain amino acid breakdown in NDD stage 5 CKD, shedding light on cellular energy production and offering insights for further clinical validation.
慢性肾脏病（CKD）影响着全球约12%的人口，对健康构成重大威胁。炎症在非透析依赖（NDD）5期CKD的尿毒症表型中起关键作用，导致受影响个体的心血管疾病发生率和总体死亡率升高。本研究旨在使用半靶向代谢组学探索该人群中的新型代谢途径，这使我们能够通过内部极性化合物库在数据采集前对众多已知身份的代谢物进行定量。在一项针对50名患者的前瞻性观察性设计中，对首次血液透析治疗前采集的血样进行液相色谱和高分辨率质谱分析。单变量（曼-惠特尼检验）和多变量（带LASSO正则化的逻辑回归）方法确定了与炎症相关的代谢组学变量。值得注意的是，5'-磷酸腺苷硫酸酯（APS）、二甲基甘氨酸、丙酮酸、乳酸和2-酮丁酸在炎症存在时表现出显著差异。胆酸、尿黑酸和2-苯丙酸呈现相反的模式。多变量分析表明，某些代谢物（丁酰甘氨酸、二甲基甘氨酸、2-氧代异戊酸和丙酮酸）会增加炎症风险，而其他代谢物（尿黑酸、2-苯丙酸和2-甲基戊二酸）则表明炎症发生概率降低。这些发现揭示了与NDD 5期CKD中线粒体脂肪酸β氧化缺陷和支链氨基酸分解相关的潜在炎症相关生物标志物，阐明了细胞能量产生情况，并为进一步的临床验证提供了见解。
