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检测发生包裹性腹膜硬化患者腹膜透析流出液代谢变化的原理验证研究。

Proof-of-principle study to detect metabolic changes in peritoneal dialysis effluent in patients who develop encapsulating peritoneal sclerosis.

作者信息

Dunn Warwick B, Summers Angela, Brown Marie, Goodacre Royston, Lambie Mark, Johnson Tim, Wilkie Martin, Davies Simon, Topley Nick, Brenchley Paul

机构信息

Manchester Centre for Integrative Systems Biology and School of Chemistry, Manchester Interdisciplinary Biocentre, University of Manchester, Manchester, UK.

出版信息

Nephrol Dial Transplant. 2012 Jun;27(6):2502-10. doi: 10.1093/ndt/gfr662. Epub 2012 Jan 31.

Abstract

BACKGROUND

Prolonged peritoneal dialysis (PD) therapy can result in the development of encapsulating peritoneal sclerosis (EPS), characterized by extensive sclerosis of the peritoneum with bowel adhesions often causing obstruction.

METHODS

As a proof-of-principle study, holistic profiling of endogenous metabolites has been applied in a prospective collection of PD effluent collected in multiple UK renal centres over 6 years in order to investigate metabolic differences in PD effluent between PD therapy patients who later developed clinically defined EPS (n = 11) and controls, who were matched for PD vintage, age and gender (n = 11).

RESULTS

'Fit-for-purpose' analytical methods employing gas chromatography-mass spectrometry (MS), direct injection MS and quality control samples were developed and validated. These methods were applied in a proof-of-principle study to define metabolic differences in PD effluent related to subsequent development of EPS. Changes in amino acids, amines and derivatives, short-chain fatty acids and derivatives and sugars were observed prior to EPS developing, and changes in the metabolomic profiles could be detected.

CONCLUSION

There is potential for applying metabolic profiles to identify patients at risk of developing EPS although long-term prospective studies with larger patient cohorts are required.

摘要

背景

长期腹膜透析(PD)治疗可导致包裹性腹膜硬化(EPS)的发生,其特征为腹膜广泛硬化,伴有肠粘连,常引起肠梗阻。

方法

作为一项原理验证研究,对来自英国多个肾脏中心6年间前瞻性收集的PD流出液进行内源性代谢物的整体分析,以调查后来发展为临床定义的EPS的PD治疗患者(n = 11)与按PD透析时间、年龄和性别匹配的对照组(n = 11)之间PD流出液的代谢差异。

结果

开发并验证了采用气相色谱 - 质谱联用(MS)、直接进样质谱和质量控制样品的“适用”分析方法。这些方法被应用于一项原理验证研究,以确定与EPS后续发展相关的PD流出液中的代谢差异。在EPS发生之前观察到氨基酸、胺及其衍生物、短链脂肪酸及其衍生物和糖类的变化,并且可以检测到代谢组学谱的变化。

结论

应用代谢谱识别有发生EPS风险的患者具有潜力,尽管需要对更大患者队列进行长期前瞻性研究。

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