Distinct metabolic profile of primary focal segmental glomerulosclerosis revealed by NMR-based metabolomics.

Distinct metabolic profile of primary focal segmental glomerulosclerosis revealed by NMR-based metabolomics.
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基于 NMR 的代谢组学揭示了原发性局灶节段性肾小球硬化的独特代谢特征

DOI:
10.1371/journal.pone.0078531
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Chen N
Chen N
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hao X;Liu X;Wang W;Ren H;Xie J;Shen P;Lin D;Chen N

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原发性局灶节段性肾小球硬化(FSGS)是一种以特发性类固醇抵抗性肾病综合征(SRNS)为特征的病理实体,在大多数患者中进展为终末期肾病(ESRD)。目前,还没有实用的无创技术来预测不同病理类型的肾小球病变。本研究探讨了尿代谢组学在FSGS诊断和发病机制中的作用。方法采用核磁共振代谢组学方法对FSGS (n = 25)、膜性肾病(MN, n = 24)、微小变化肾病(MCD, n = 14)、IgA肾病(IgAN, n = 26)及健康对照(CON, n = 35)患者的尿液代谢谱进行分析。采用主成分分析(PCA)和正交投影潜结构判别分析(OPLS-DA)对采集数据进行分析。采用置换检验验证模型的有效性。结果FSGS患者与健康对照组及其他三种肾小球病变有明显区别,具有良好的敏感性和特异性。与健康对照组相比,FSGS患者尿中葡萄糖、二甲胺和三甲胺水平升高,而丙酮酸、缬氨酸、马尿酸、异亮氨酸、苯乙酰甘氨酸、柠檬酸、酪氨酸、3-甲基组氨酸和β-羟基异戊酸降低。此外,与其他肾小球疾病相比,FSGS患者的尿n -甲基烟酰胺水平较低。结论基于核磁共振的代谢组学方法可用于FSGS及其他肾小球疾病的无创诊断和鉴别诊断,并提示原发性FSGS的可能机制。
Background Primary focal segmental glomerulosclerosis (FSGS) is pathological entity which is characterized by idiopathic steroid-resistant nephrotic syndrome (SRNS) and progression to end-stage renal disease (ESRD) in the majority of affected individuals. Currently, there is no practical noninvasive technique to predict different pathological types of glomerulopathies. In this study, the role of urinary metabolomics in the diagnosis and pathogenesis of FSGS was investigated. Methods NMR-based metabolomics was applied for the urinary metabolic profile in the patients with FSGS (n = 25), membranous nephropathy (MN, n = 24), minimal change disease (MCD, n = 14) and IgA nephropathy (IgAN, n = 26), and healthy controls (CON, n = 35). The acquired data were analyzed using principal component analysis (PCA) followed by orthogonal projections to latent structure discriminant analysis (OPLS-DA). Model validity was verified using permutation tests. Results FSGS patients were clearly distinguished from healthy controls and other three types of glomerulopathies with good sensitivity and specificity based on their global urinary metabolic profiles. In FSGS patients, urinary levels of glucose, dimethylamine and trimethylamine increased compared with healthy controls, while pyruvate, valine, hippurate, isoleucine, phenylacetylglycine, citrate, tyrosine, 3-methylhistidine and β-hydroxyisovalerate decreased. Additionally, FSGS patients had lower urine N-methylnicotinamide levels compared with other glomerulopathies. Conclusions NMR-based metabonomic approach is amenable for the noninvasive diagnosis and differential diagnosis of FSGS as well as other glomerulopathies, and it could indicate the possible mechanisms of primary FSGS.
基于核磁共振的代谢组学方法揭示了创伤性危重患者的全身代谢变化。
DOI: 10.1021/pr900576y
发表时间: 2009-12-01
影响因子: 4.4
作者:
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期刊: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
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DOI: 10.1371/journal.pone.0025563
发表时间: 2011
期刊: PloS one
影响因子: 3.7
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DOI: 10.1159/000186698
发表时间: 1992-01-01
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影响因子: 2.5
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