Evaluation of urinary volatile organic compounds as a novel metabolomic biomarker to assess chronic kidney disease progression.

IF 2.2 4区 医学 Q2 UROLOGY & NEPHROLOGY
Henry H L Wu, Malcolm Possell, Long The Nguyen, Wenbo Peng, Carol A Pollock, Sonia Saad
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引用次数: 0

Abstract

Background: There is a need to develop accurate and reliable non-invasive methods to evaluate chronic kidney disease (CKD) status and assess disease progression. Given it is recognized that dysregulation in metabolic pathways occur from early CKD, there is a basis in utilizing metabolomic biomarkers to monitor CKD progression. Volatile Organic Compounds (VOCs), a form of metabolomic biomarker, are gaseous products of metabolic processes in organisms which are typically released with greater abundance in disease conditions when there is dysregulation in metabolism. How urinary VOCs reflect the abnormal metabolic profile of patients with CKD status is unknown. Our study aimed to explore this.

Methods: Individuals aged 18-75 years undergoing kidney biopsy were included. Pre-biopsy urine samples were collected. All biopsy samples had an interstitial fibrosis and tubular atrophy (IFTA) grade scored by standardized assessment. Urine supernatant was extracted from residue and sampled for stir bar sorptive extraction followed by Gas chromatography-mass spectrometry (GC-MS) analysis. Post-processing of GC-MS data separated complex mixtures of VOCs based on their volatility and polarity. Mass-to-charge ratios and fragment patterns were measured for individual VOCs identification and quantification. Linear discriminant analysis (LDA) was performed to assess the ability of urinary VOCs in discriminating between IFTA 0 ('no or minimal IFTA' i.e. <10%, IFTA), IFTA 1 ('mild IFTA' i.e. 10-25% IFTA) and IFTA ≥ 2 ('moderate or severe IFTA' i.e. >25% IFTA). Linear regression analysis adjusting for age, sex, estimated glomerular filtration rate, diabetes mellitus (DM) status, and albuminuria was conducted to determine significantly regulated urinary VOCs amongst the groups.

Results: 64 study participants (22 individuals IFTA 0, 15 individuals IFTA 1, 27 individuals IFTA ≥ 2) were included. There were 34 VOCs identified from GC-MS which were statistically associated with correct classification between the IFTA groups, and LDA demonstrated individuals with IFTA 0, IFTA 1 and IFTA ≥ 2 could be significantly separated by their urinary VOCs profile (p < 0.001). Multivariate linear regression analysis reported 4 VOCs significantly upregulated in the IFTA 1 compared to the IFTA 0 group, and 2 VOCs significantly upregulated in the IFTA ≥ 2 compared to the IFTA 1 group (p < 0.05). Significantly upregulated urinary VOCs belonged to one of four functional groups - aldehydes, ketones, hydrocarbons, or alcohols.

Conclusions: We report novel links between urinary VOCs and tubulointerstitial histopathology. Our findings suggest the application of urinary VOCs as a metabolomic biomarker may have a useful clinical role to non-invasively assess CKD status during disease progression.

将尿挥发性有机化合物作为一种新型代谢组学生物标记物来评估慢性肾脏病的进展。
背景:需要开发准确可靠的非侵入性方法来评估慢性肾脏病(CKD)的状态和疾病进展。鉴于人们认识到代谢途径的失调从 CKD 早期就开始出现,因此利用代谢组生物标志物监测 CKD 的进展是有依据的。挥发性有机化合物(VOCs)是代谢组生物标志物的一种形式,是生物体内代谢过程的气态产物,通常在新陈代谢失调的疾病情况下会大量释放。尿液中的挥发性有机化合物如何反映出慢性肾脏病患者代谢异常的情况尚不清楚。我们的研究旨在探讨这一问题:方法:纳入接受肾活检的 18-75 岁个体。收集活检前的尿液样本。所有活检样本均通过标准化评估进行间质纤维化和肾小管萎缩(IFTA)分级。从残留物中提取尿液上清液并取样进行搅拌棒吸附萃取,然后进行气相色谱-质谱(GC-MS)分析。气相色谱-质谱数据的后处理根据挥发性和极性分离出复杂的挥发性有机化合物混合物。通过测量质量电荷比和片段模式来识别和定量单个挥发性有机化合物。进行了线性判别分析(LDA),以评估尿液挥发性有机化合物在区分 IFTA 0("无或极少 IFTA",即 25% IFTA)方面的能力。在对年龄、性别、估计肾小球滤过率、糖尿病(DM)状态和白蛋白尿进行调整后,进行了线性回归分析,以确定各组间显著调节的尿液挥发性有机化合物:共纳入 64 名研究人员(22 人 IFTA 0,15 人 IFTA 1,27 人 IFTA ≥ 2)。通过 GC-MS 鉴定出的 34 种挥发性有机化合物在统计学上与 IFTA 组间的正确分类有关,LDA 表明 IFTA 0、IFTA 1 和 IFTA ≥ 2 的个体可通过其尿液挥发性有机化合物特征显著区分开来(p 结论:我们报告了尿液挥发性有机化合物与 IFTA 组间的新联系:我们报告了尿中挥发性有机化合物与肾小管间质组织病理学之间的新联系。我们的研究结果表明,应用尿液中的挥发性有机化合物作为代谢组学生物标记物,可在疾病进展过程中对 CKD 状态进行非侵入性评估,具有有用的临床作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
BMC Nephrology
BMC Nephrology UROLOGY & NEPHROLOGY-
CiteScore
4.30
自引率
0.00%
发文量
375
审稿时长
3-8 weeks
期刊介绍: BMC Nephrology is an open access journal publishing original peer-reviewed research articles in all aspects of the prevention, diagnosis and management of kidney and associated disorders, as well as related molecular genetics, pathophysiology, and epidemiology.
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