Use of serum and urine metabolome analysis for the detection of metabolic changes in patients with stage 1-2 chronic kidney disease
Use of serum and urine metabolome analysis for the detection of metabolic changes in patients with stage 1-2 chronic kidney disease
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发表时间：
2011
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通讯作者：
Kaori Hayashi;H. Sasamura;T. Hishiki;M. Suematsu;Satsuki Ikeda;T. Soga;H. Itoh
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作者：
Kaori Hayashi;H. Sasamura;T. Hishiki;M. Suematsu;Satsuki Ikeda;T. Soga;H. Itoh
背景资料：慢性肾脏病（CKD）是世界范围内的主要健康问题，了解CKD的病理状态变得越来越重要。近年来，随着代谢组学技术的发展，人们可以对人体代谢状况进行灵敏、全面的评价。目的：本研究的目的是使用代谢组学分析进行初步调查的代谢变化发生在1-2期CKD患者。患者和方法：采用毛细管电泳-飞行时间质谱（CE-TOFMS）系统分析了15例1-2期CKD患者的血清和尿液代谢谱，并与7例健康志愿者进行了比较。结果如下：CE-TOFMS系统在三种不同模式下进行阳离子、阴离子和核苷酸分析，可检测血清和尿液样本中的多种代谢物。在阳离子分析模式中，在1-2期CKD患者中发现了几种非必需氨基酸的增加，与终末期肾病（ESRD）报告的结果相似。自由基清除剂肌肽和亚牛磺酸在尿液中减少，而血清亚牛磺酸和牛磺酸增加，与肾脏和/或全身氧化应激的变化一致。此外，心脏毒素次黄嘌呤在血清中显着增加，而血清和尿腺苷和尿鸟嘌呤减少，提示嘌呤核苷酸代谢的变化，可能会影响心血管预后。还检测到其他未鉴别代谢物的变化。结论：这些结果表明，在1-2期CKD中，使用代谢组学分析已经可以检测到多种代谢变化。对这些代谢变化的进一步研究可能会产生新的策略，以预防CKD患者的心血管事件和进展为ESRD。产品信息
Background: Chronic kidney disease (CKD) is a major health problem throughout the world, and understanding the pathological condition of CKD has become increasingly important. The recent development of advanced metabolomic assay techniques now allows the human metabolic condition to be evaluated sensitively and comprehensively. Objectives: The aim of this study was to use metabolomic analysis to perform a preliminary survey of metabolic changes occurring in patients with stage 1-2 CKD. Patients and Methods: Serum and urine metabolomic profiles of 15 patients with stage 1-2 CKD were analyzed using our previously reported capillary electrophoresis time-offlight mass spectrometry (CE-TOFMS) systems, and compared to 7 healthy volunteers. Results: The CE-TOFMS systems in three different modes for cation, anion, and nucleotide analyses detected multiple metabolites in serum and urine samples. In cation analysis mode, several increases in nonessential amino acids were identified in patients with stage 1-2 CKD, similar to those reported for end-stage renal disease (ESRD). Free-radical scavengers carnosine and hypotaurine were decreased in the urine, whereas serum hypotaurine and taurine were increased, consistent with changes in renal and/or systemic oxidative stress. Moreover, the cardiotoxin hypoxanthine was markedly increased in the serum, whereas serum and urine adenosine and urine guanine were decreased, suggesting changes in purine nucleotide metabolism which could affect cardiovascular prognosis. Changes in other unidentified metabolites were also detected. Conclusions: These results suggest that multiple changes in the metabolism are already detectable in stage 1-2 CKD using metabolome analysis. Further studies on these metabolic changes may result in new strategies to prevent cardiovascular events and progression to ESRD in patients with CKD. ARTICLE INFO