Yu Yipin, Yi Qiong, Yang Chenglong, Song Xudong, Tan Duoting, Peng Qinghua, Sun Xiang, Liang Hao
Institute of TCM Diagnostics, Hunan University of Chinese Medicine, 410208 Changsha, Hunan, China.
ICU Department, The First Hospital of Hunan University of Chinese Medicine, 410021 Changsha, Hunan, China.
Rev Cardiovasc Med. 2025 Apr 22;26(4):27001. doi: 10.31083/RCM27001. eCollection 2025 Apr.
Diuretic resistance (DR) is characterized by insufficient fluid and sodium excretion enhancement despite maximum loop diuretic doses, indicating a phenotype of refractory heart failure (HF). Recently, metabolomics has emerged as a crucial tool for diagnosing and understanding the pathogenesis of various diseases. This study aimed to differentiate diuretic-resistant patients from non-resistant HF to identify biomarkers linked to the emergence of DR.
Serum samples from HF patients, both with and without DR, were subjected to non-targeted metabolomic analysis using liquid chromatography-tandem mass spectrometry. Metabolite variations between groups were identified using principal component analysis and orthogonal partial least-square discriminant analysis. Metabolic pathways were assessed through the Kyoto Encyclopedia of Genes and Genomes database enrichment analysis, and potential biomarkers were determined using receiver operating characteristic curves (ROCs).
In total, 192 metabolites exhibited significant differences across the two sample groups. Among these, up-regulation was observed in 164 metabolites, while 28 metabolites were down-regulated. A total of 28 pathways involving neuroactive ligand-receptor interaction and amino acid biosynthesis were affected. The top five metabolites identified by ROC analysis as potential DR biomarkers were hydroxykynurenine, perillic acid, adrenic acid, 5-acetamidovalerate, and adipic acid.
Significant differences in metabolite profiles were observed between the diuretic-resistant and non-diuretic-resistant groups among patients with HF. The top five differentially expressed endogenous metabolites were hydroxykynurenine, perillic acid, adrenic acid, 5-acetamidovalerate, and adipic acid. The metabolic primary pathways implicated in DR were noted as amino acid, energy, and nucleotide metabolism.
This study was registered with the China Clinical Trials Registry (https://www.chictr.org.cn/hvshowproject.html?id=197183&v=1.7, ChiCTR2100053587).
利尿剂抵抗（DR）的特征是尽管使用了最大剂量的襻利尿剂，但体液和钠排泄增强不足，这表明为难治性心力衰竭（HF）的一种表型。近来，代谢组学已成为诊断和理解各种疾病发病机制的关键工具。本研究旨在区分利尿剂抵抗患者与非抵抗性心力衰竭患者，以确定与利尿剂抵抗出现相关的生物标志物。
对有和没有利尿剂抵抗的心力衰竭患者的血清样本进行非靶向代谢组学分析，采用液相色谱 - 串联质谱法。使用主成分分析和正交偏最小二乘判别分析确定组间代谢物差异。通过京都基因与基因组百科全书数据库富集分析评估代谢途径，并使用受试者工作特征曲线（ROC）确定潜在的生物标志物。
总共192种代谢物在两个样本组之间表现出显著差异。其中，164种代谢物上调，28种代谢物下调。共有28条涉及神经活性配体 - 受体相互作用和氨基酸生物合成的途径受到影响。通过ROC分析确定为潜在DR生物标志物的前五种代谢物是羟基犬尿氨酸、紫苏酸、肾上腺酸、5 - 乙酰氨基戊酸和己二酸。
心力衰竭患者中，利尿剂抵抗组和非利尿剂抵抗组之间观察到代谢物谱存在显著差异。差异表达的前五种内源性代谢物是羟基犬尿氨酸、紫苏酸、肾上腺酸、5 - 乙酰氨基戊酸和己二酸。与利尿剂抵抗相关的主要代谢途径被指出为氨基酸、能量和核苷酸代谢。
本研究已在中国临床试验注册中心注册（https://www.chictr.org.cn/hvshowproject.html?id=197183&v=1.7, ChiCTR2100053587）。
