Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Institut d'Investigacions Biomètiques August Pi i Sunyer (IDIBAPS), 08027 Barcelona, Spain.
Red de Investigación Cooperativa Orientada a Resultados en Salud (RICORS 2040), 28029 Madrid, Spain.
Nutrients. 2024 Oct 31;16(21):3739. doi: 10.3390/nu16213739.
Cardiovascular disease (CVD) remains the most common cause of mortality in chronic kidney disease (CKD) patients. Several studies suggest that the Mediterranean diet reduces the risk of CVD due to its influence on endothelial function, inflammation, lipid profile, and blood pressure. Integrating metabolomic and proteomic analyses of CKD could provide insights into the pathways involved in uremia-induced CVD and those pathways modifiable by the Mediterranean diet.
We performed metabolomic and proteomic analyses on serum samples from 19 patients with advanced CKD (aCKD) and 27 healthy volunteers. The metabolites were quantified using four different approaches, based on their properties. Proteomic analysis was performed after depletion of seven abundant serum proteins (Albumin, IgG, antitrypsin, IgA, transferrin, haptoglobin, and fibrinogen). Integrative analysis was performed using MetaboAnalyst 4.0 and STRING 11.0 software to identify the dysregulated pathways and biomarkers.
A total of 135 metabolites and 75 proteins were differentially expressed in aCKD patients, compared to the controls. Pathway enrichment analysis showed significant alterations in the innate immune system pathways, including complement, coagulation, and neutrophil degranulation, along with disrupted linoleic acid and cholesterol metabolism. Additionally, certain key metabolites and proteins were altered in aCKD patients, such as glutathione peroxidase 3, carnitine, homocitrulline, 3-methylhistidine, and several amino acids and derivatives.
Our findings reveal significant dysregulation of the serum metabolome and proteome in aCKD, particularly in those pathways associated with endothelial dysfunction and CVD. These results suggest that CVD prevention in CKD may benefit from a multifaceted approach, including dietary interventions such as the Mediterranean diet.
心血管疾病（CVD）仍然是慢性肾脏病（CKD）患者死亡的最常见原因。有几项研究表明，地中海饮食通过影响内皮功能、炎症、血脂谱和血压，降低 CVD 的风险。整合 CKD 的代谢组学和蛋白质组学分析，可以深入了解尿毒症引起的 CVD 相关途径以及地中海饮食可调节的途径。
我们对 19 名晚期 CKD（aCKD）患者和 27 名健康志愿者的血清样本进行了代谢组学和蛋白质组学分析。根据其性质，使用四种不同的方法对代谢物进行定量。在耗尽七种丰富的血清蛋白（白蛋白、IgG、抗胰蛋白酶、IgA、转铁蛋白、触珠蛋白和纤维蛋白原）后，进行蛋白质组学分析。使用 MetaboAnalyst 4.0 和 STRING 11.0 软件进行综合分析，以识别失调的途径和生物标志物。
与对照组相比，aCKD 患者的 135 种代谢物和 75 种蛋白质表达差异。通路富集分析显示，先天免疫系统途径（包括补体、凝血和嗜中性粒细胞脱颗粒）发生了显著改变，同时还存在亚油酸和胆固醇代谢紊乱。此外，aCKD 患者的某些关键代谢物和蛋白质发生了改变，如谷胱甘肽过氧化物酶 3、肉碱、同型瓜氨酸、3-甲基组氨酸和几种氨基酸及其衍生物。
我们的研究结果表明，aCKD 患者的血清代谢组和蛋白质组存在显著失调，特别是与内皮功能障碍和 CVD 相关的途径。这些结果表明，CKD 的 CVD 预防可能受益于多方面的方法，包括地中海饮食等饮食干预。
