Application of Metabolomics and the Discovery of Potential Serum Biomarkers for Diuretic Resistance in Heart Failure
Background: 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 unders...
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| Format: | Article |
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IMR Press
2025-04-01
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| Series: | Reviews in Cardiovascular Medicine |
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| Online Access: | https://www.imrpress.com/journal/RCM/26/4/10.31083/RCM27001 |
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| author | Yipin Yu Qiong Yi Chenglong Yang Xudong Song Duoting Tan Qinghua Peng Xiang Sun Hao Liang |
| author_facet | Yipin Yu Qiong Yi Chenglong Yang Xudong Song Duoting Tan Qinghua Peng Xiang Sun Hao Liang |
| author_sort | Yipin Yu |
| collection | DOAJ |
| description | Background: 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. Methods: 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). Results: 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. Conclusions: 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. Clinical Trial Registration: This study was registered with the China Clinical Trials Registry (https://www.chictr.org.cn/hvshowproject.html?id=197183&v=1.7, ChiCTR2100053587). |
| format | Article |
| id | doaj-art-51bbb4172c8b4cb480084c211674f060 |
| institution | OA Journals |
| issn | 1530-6550 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | IMR Press |
| record_format | Article |
| series | Reviews in Cardiovascular Medicine |
| spelling | doaj-art-51bbb4172c8b4cb480084c211674f0602025-08-20T02:28:55ZengIMR PressReviews in Cardiovascular Medicine1530-65502025-04-012642700110.31083/RCM27001S1530-6550(25)01756-9Application of Metabolomics and the Discovery of Potential Serum Biomarkers for Diuretic Resistance in Heart FailureYipin Yu0Qiong Yi1Chenglong Yang2Xudong Song3Duoting Tan4Qinghua Peng5Xiang Sun6Hao Liang7Institute of TCM Diagnostics, Hunan University of Chinese Medicine, 410208 Changsha, Hunan, ChinaICU Department, The First Hospital of Hunan University of Chinese Medicine, 410021 Changsha, Hunan, ChinaCardiovascular Department, The First Hospital of Hunan University of Chinese Medicine, 410021 Changsha, Hunan, ChinaInstitute of TCM Diagnostics, Hunan University of Chinese Medicine, 410208 Changsha, Hunan, ChinaInstitute of TCM Diagnostics, Hunan University of Chinese Medicine, 410208 Changsha, Hunan, ChinaHunan Provincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese Medicine, 410208 Changsha, Hunan, ChinaCardiology Department, Changsha Hospital of Chinese Medicine, 410001 Changsha, Hunan, ChinaHunan Provincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese Medicine, 410208 Changsha, Hunan, ChinaBackground: 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. Methods: 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). Results: 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. Conclusions: 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. Clinical Trial Registration: This study was registered with the China Clinical Trials Registry (https://www.chictr.org.cn/hvshowproject.html?id=197183&v=1.7, ChiCTR2100053587).https://www.imrpress.com/journal/RCM/26/4/10.31083/RCM27001heart failurediuretic resistancemetabolomicbiomarker |
| spellingShingle | Yipin Yu Qiong Yi Chenglong Yang Xudong Song Duoting Tan Qinghua Peng Xiang Sun Hao Liang Application of Metabolomics and the Discovery of Potential Serum Biomarkers for Diuretic Resistance in Heart Failure Reviews in Cardiovascular Medicine heart failure diuretic resistance metabolomic biomarker |
| title | Application of Metabolomics and the Discovery of Potential Serum Biomarkers for Diuretic Resistance in Heart Failure |
| title_full | Application of Metabolomics and the Discovery of Potential Serum Biomarkers for Diuretic Resistance in Heart Failure |
| title_fullStr | Application of Metabolomics and the Discovery of Potential Serum Biomarkers for Diuretic Resistance in Heart Failure |
| title_full_unstemmed | Application of Metabolomics and the Discovery of Potential Serum Biomarkers for Diuretic Resistance in Heart Failure |
| title_short | Application of Metabolomics and the Discovery of Potential Serum Biomarkers for Diuretic Resistance in Heart Failure |
| title_sort | application of metabolomics and the discovery of potential serum biomarkers for diuretic resistance in heart failure |
| topic | heart failure diuretic resistance metabolomic biomarker |
| url | https://www.imrpress.com/journal/RCM/26/4/10.31083/RCM27001 |
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