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呼吸分析:鉴定潜在挥发性生物标志物用于非侵入性诊断慢性肾脏病(CKD)。

Breath Analysis: Identification of Potential Volatile Biomarkers for Non-Invasive Diagnosis of Chronic Kidney Disease (CKD).

机构信息

Department of Bioscience, Biotechnologies and Environment, University of Bari, 70126 Bari, Italy.

Apulian Breath Analysis Center (CeRBA), IRCCS Giovanni Paolo II, 70124 Bari, Italy.

出版信息

Molecules. 2024 Oct 2;29(19):4686. doi: 10.3390/molecules29194686.

DOI:10.3390/molecules29194686
PMID:39407614
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11477747/
Abstract

Recently, volatile organic compound (VOC) determination in exhaled breath has seen growing interest due to its promising potential in early diagnosis of several pathological conditions, including chronic kidney disease (CKD). Therefore, this study aimed to identify the breath VOC pattern providing an accurate, reproducible and fast CKD diagnosis at early stages of disease. A cross-sectional observational study was carried out, enrolling a total of 30 subjects matched for age and gender. More specifically, the breath samples were collected from (a) 10 patients with end-stage kidney disease (ESKD) before undergoing hemodialysis treatment (DIAL); (b) 10 patients with mild-moderate CKD (G) including 3 patients in stage G2 with mild albuminuria, and 7 patients in stage G3 and (c) 10 healthy controls (CTRL). For each volunteer, an end-tidal exhaled breath sample and an ambient air sample (AA) were collected at the same time on two sorbent tubes by an automated sampling system and analyzed by Thermal Desorption-Gas Chromatography-Mass Spectrometry. A total of 110 VOCs were detected in breath samples but only 42 showed significatively different levels with respect to AA. Nonparametric tests, such as Wilcoxon/Kruskal-Wallis tests, allowed us to identify the most weighting variables able to discriminate between AA, DIAL, G and CTRL breath samples. A promising multivariate data mining approach incorporating only selected variables (showing -values lower than 0.05), such as nonanal, pentane, acetophenone, pentanone, undecane, butanedione, ethyl hexanol and benzene, was developed and cross-validated, providing a prediction accuracy equal to 87% and 100% in identifying patients with both mild-moderate CKD (G) and ESKD (DIAL), respectively.

摘要

最近,由于呼气挥发性有机化合物 (VOC) 分析在几种病理情况下的早期诊断中具有很大的应用潜力,包括慢性肾脏病 (CKD),因此受到了越来越多的关注。因此,本研究旨在确定一种准确、可重现且快速的 VOC 分析方法,以早期诊断 CKD。本研究采用了横断面观察性研究方法,共纳入 30 名年龄和性别匹配的受试者。具体来说,采集了以下三组受试者的呼气样本:(a)10 名即将开始血液透析治疗的终末期肾病(ESKD)患者(DIAL);(b)10 名患有轻度至中度 CKD(G)的患者,包括 3 名轻度白蛋白尿的 G2 期患者和 7 名 G3 期患者;(c)10 名健康对照者(CTRL)。对于每位志愿者,在同一时间通过自动采样系统,使用两个吸附管同时采集呼气终末呼出样本和环境空气样本(AA),然后用热解吸-气相色谱-质谱法进行分析。在呼气样本中检测到了 110 种 VOC,但只有 42 种与 AA 相比显示出显著差异。非参数检验(如 Wilcoxon/Kruskal-Wallis 检验)允许我们确定能够区分 AA、DIAL、G 和 CTRL 呼吸样本的最有意义的变量。采用了一种很有前途的多元数据挖掘方法,仅纳入了一些具有统计学意义的变量(p 值小于 0.05),如壬醛、戊烷、苯乙酮、戊酮、十一烷、丁二酮、正己醇和苯,对其进行了交叉验证,在识别患有轻度至中度 CKD(G)和 ESKD(DIAL)的患者方面,该方法的预测准确率分别为 87%和 100%。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2214/11477747/3953f6848e87/molecules-29-04686-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2214/11477747/b5140a979572/molecules-29-04686-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2214/11477747/6e23d201466b/molecules-29-04686-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2214/11477747/c1d25a746b24/molecules-29-04686-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2214/11477747/3953f6848e87/molecules-29-04686-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2214/11477747/b5140a979572/molecules-29-04686-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2214/11477747/6e23d201466b/molecules-29-04686-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2214/11477747/c1d25a746b24/molecules-29-04686-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2214/11477747/3953f6848e87/molecules-29-04686-g004.jpg

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本文引用的文献

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KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease.KDIGO 2024慢性肾脏病评估与管理临床实践指南
Kidney Int. 2024 Apr;105(4S):S117-S314. doi: 10.1016/j.kint.2023.10.018.
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Metabolites. 2023 Jul 11;13(7):837. doi: 10.3390/metabo13070837.
3
Identification of a characteristic VOCs pattern in the exhaled breath of post-COVID subjects: are metabolic alterations induced by the infection still detectable?
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J Breath Res. 2023 Jul 12;17(4). doi: 10.1088/1752-7163/ace27c.
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Smelling the Disease: Diagnostic Potential of Breath Analysis.嗅探疾病:呼吸分析的诊断潜力。
Mol Diagn Ther. 2023 May;27(3):321-347. doi: 10.1007/s40291-023-00640-7. Epub 2023 Feb 2.
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Utility of SIFT-MS to evaluate volatile organic compounds in nephropathic patients' breath.SIFT-MS 在评估肾病人群呼出气中挥发性有机化合物的应用。
Sci Rep. 2022 Jun 21;12(1):10413. doi: 10.1038/s41598-022-14152-7.
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Breath Analysis: Comparison among Methodological Approaches for Breath Sampling.呼吸分析:呼吸采样方法学方法比较。
Molecules. 2020 Dec 10;25(24):5823. doi: 10.3390/molecules25245823.
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PLoS One. 2020 May 29;15(5):e0233331. doi: 10.1371/journal.pone.0233331. eCollection 2020.
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