Volatile Organic Metabolites Identify Patients with Mesangial Proliferative Glomerulonephritis, IgA Nephropathy and Normal Controls

Wang, Changsong; Feng, Yue; Wang, Mingao; Pi, Xin; Tong, Hongshuang; Wang, Yue; Zhu, Lin; Li, Enyou

doi:10.1038/srep14744

Cited by 14 publications

(10 citation statements)

References 25 publications

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“…Metabolomics platforms now enable the simultaneous measurement of hundreds of small molecular metabolites describing the downstream effects of genes and proteins. Patients with glomerulonephritis,7, 8, 9 kidney transplantation,10, 11 diabetes nephropathy, 12 acute kidney injury, 13 and general CKD14, 15, 16, 17 have been studied, and important disturbances in amino acid, glucose, and fatty acid metabolism as well as the central energy metabolism have been described 12, 18, 19. Whether this extends to patients with hypertensive nephrosclerosis is not well studied.…”

mentioning

confidence: 99%

Gene Expression Studies and Targeted Metabolomics Reveal Disturbed Serine, Methionine, and Tyrosine Metabolism in Early Hypertensive Nephrosclerosis

Øvrehus

Bruheim

et al. 2019

Kidney International Reports

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IntroductionHypertensive nephrosclerosis is among the leading causes of end-stage renal disease, but its pathophysiology is poorly understood. We wanted to explore early metabolic changes using gene expression and targeted metabolomics analysis.MethodsWe analyzed gene expression in kidneys biopsied from 20 patients with nephrosclerosis and 31 healthy controls with an Affymetrix array. Thirty-one amino acids were measured by liquid chromatography coupled with mass spectrometry (LC-MS) in urine samples from 62 patients with clinical hypertensive nephrosclerosis and 33 age- and sex-matched healthy controls, and major findings were confirmed in an independent cohort of 45 cases and 15 controls.ResultsAmino acid catabolism and synthesis were strongly underexpressed in hypertensive nephrosclerosis (13- and 7-fold, respectively), and these patients also showed gene expression patterns indicating decreased fatty acid oxidation (12-fold) and increased interferon gamma (10-fold) and cellular defense response (8-fold). Metabolomics analysis revealed significant distribution differences in 11 amino acids in hypertensive nephrosclerosis, among them tyrosine, phenylalanine, dopamine, homocysteine, and serine, with 30% to 70% lower urine excretion. These findings were replicated in the independent cohort. Integrated gene-metabolite pathway analysis showed perturbations of renal dopamine biosynthesis. There were also significant differences in homocysteine/methionine homeostasis and the serine pathway, which have strong influence on 1-carbon metabolism. Several of these disturbances could be interconnected through reduced regeneration of tetrahydrofolate and tetrahydrobiopterin.ConclusionEarly hypertensive nephrosclerosis showed perturbations of intrarenal biosynthesis of dopamine, which regulates natriuresis and blood pressure. There were also disturbances in serine/glycine and methionine/homocysteine metabolism, which may contribute to endothelial dysfunction, atherosclerosis, and renal fibrosis.

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confidence: 99%

Gene Expression Studies and Targeted Metabolomics Reveal Disturbed Serine, Methionine, and Tyrosine Metabolism in Early Hypertensive Nephrosclerosis

Øvrehus

Bruheim

et al. 2019

Kidney International Reports

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“…44 Urinary metabolomics studies have been employed to different cancer studies, such as breast, colorectal, esophageal, pancreatic ductal adenocarcinoma, prostate, and liver cancers. 45 Analyzing four different VOCs (2,6-dimethyl-7-octen-2ol, pentanal, 3-octanone, and 2-octanone), Khalid et al demonstrated the detection of prostate cancer. 46 Matsumura et al demonstrated ex-vivo analysis of urinary VOCs as biomarkers for lung cancer.…”

Section: ■ Sources For Invasive Detectionmentioning

confidence: 99%

“…Elevated levels of acetonitrile in urine confirms whether someone is a smoker or not . Urinary metabolomics studies have been employed to different cancer studies, such as breast, colorectal, esophageal, pancreatic ductal adenocarcinoma, prostate, and liver cancers . Analyzing four different VOCs (2,6-dimethyl-7-octen-2-ol, pentanal, 3-octanone, and 2-octanone), Khalid et al demonstrated the detection of prostate cancer .…”

Section: Sources For Noninvasive Detectionmentioning

confidence: 99%

Prospects and Challenges of Volatile Organic Compound Sensors in Human Healthcare

et al. 2018

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The chemical signatures of volatile organic compounds (VOCs) in humans can be utilized for point-of-care (POC) diagnosis. Apart from toxic exposure studies, VOCs generated in humans can provide insights into one's healthy and diseased metabolic states, acting as a biomarker for identifying numerous diseases noninvasively. VOC sensors and the technology of e-nose have received significant attention for continuous and selective monitoring of various physiological and pathophysiological conditions of an individual. Noninvasive detection of VOCs is achieved from biomatrices of breath, sweat and saliva. Among these, detection from sweat and saliva can be continuous in real-time. The sensing approaches include optical, chemiresistive and electrochemical techniques. This article provides an overview of such techniques. These, however, have limitations of reliability, precision, selectivity, and stability in continuous monitoring. Such limitations are due to lack of sensor stability and complexity of samples in a multivariate environment, which can lead to false readings. To overcome selectivity barriers, sensor arrays enabling multimodal sensing, have been used with pattern recognition techniques. Stability and precision issues have been addressed through advancements in nanotechnology. The use of various forms of nanomaterial not only enhance sensing performance, but also plays a major role in detection on a miniaturized scale. The rapid growth in medical Internet of Things (IoT) and artificial intelligence paves a pathway for improvements in human theranostics.

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“…For example, solid-phase microextraction-chromatography-mass spectrometry (SPME-GC-MS) was used by Wang et al to study urinary volatile organic compounds, as a marker for pathological changes in the kidney. 110 Five urinary metabolites (tartronic acid, carbamic acid, sulfide, allyl methyl, hydrogen azide, and benzeneethanamine,N-[(pentafluorophenyl)methylene]-.beta.,4-bis[(trimethylsilyl)oxy]-), were identified and significantly increased in IgAN compared with MPGN patients. These results suggest urinary metabolites may be used as biomarkers to differentiate between different forms of GN.…”

Section: High-throughput Technologies In Gn Researchmentioning

confidence: 99%

Prospects for Precision Medicine in Glomerulonephritis Treatment

Liu

Chun

2018

Can J Kidney Health Dis

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Background:Glomerulonephritis (GN) consists of a group of kidney diseases that are categorized based on shared histopathological features. The current classifications for GN make it difficult to distinguish the individual variability in presentation, disease progression, and response to treatment. GN is a significant cause of end-stage renal disease (ESRD), and improved therapies are desperately needed because current immunosuppressive therapies sometimes lack efficacy and can lead to significant toxicities. In recent years, the combination of high-throughput genetic approaches and technological advances has identified important regulators contributing to GN.Objectives:In this review, we summarize recent findings in podocyte biology and advances in experimental approaches that have opened the possibility of precision medicine in GN treatment. We provide an integrative basic science and clinical overview of new developments in GN research and the discovery of potential candidates for targeted therapies in GN.Findings:Advances in podocyte biology have identified many candidates for therapeutic targets and potential biomarkers of glomerular disease. The goal of precision medicine in GN is now being pursued with recent technological improvements in genetics, accessibility of biologic and clinical information with tissue biobanks, high-throughput analysis of large-scale data sets, and new human model systems such as kidney organoids.Conclusion:With advances in data collection, technologies, and experimental model systems, we now have vast tools available to pursue precision medicine in GN. We anticipate a growing number of studies integrating data from high-throughput analysis with the development of diagnostic tools and targeted therapies for GN in the near future.

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Volatile Organic Metabolites Identify Patients with Mesangial Proliferative Glomerulonephritis, IgA Nephropathy and Normal Controls

Cited by 14 publications

References 25 publications

Gene Expression Studies and Targeted Metabolomics Reveal Disturbed Serine, Methionine, and Tyrosine Metabolism in Early Hypertensive Nephrosclerosis

Gene Expression Studies and Targeted Metabolomics Reveal Disturbed Serine, Methionine, and Tyrosine Metabolism in Early Hypertensive Nephrosclerosis

Prospects and Challenges of Volatile Organic Compound Sensors in Human Healthcare

Prospects for Precision Medicine in Glomerulonephritis Treatment

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