Cross-sectional examination of metabolites and metabolic phenotypes in uremia.
Cross-sectional examination of metabolites and metabolic phenotypes in uremia.
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DOI：
10.1186/s12882-015-0100-y
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发表时间：
2015-07-07
期刊：
影响因子：
2.3
通讯作者：
Rhee EP
中科院分区：
文献类型：
--
作者：
Kalim S;Clish CB;Deferio JJ;Ortiz G;Moffet AS;Gerszten RE;Thadhani R;Rhee EP
虽然代谢组学方法已经开始记录终末期肾病（ESRD）中出现的许多变化，但这些变化与尿毒症中已建立的代谢表型的关系尚不清楚。在200例血液透析患者中，我们使用偏最小二乘判别分析来确定166种代谢物中哪一种最能区分糖尿病患者和非糖尿病患者，以及体重指数、血清白蛋白、总胆固醇和收缩压的三分位数。我们的数据没有概括肾功能正常个体中发现的糖尿病和肥胖的代谢组学特征（例如支链和芳香族氨基酸升高），并强调了ESRD特有的糖尿病状态的几个潜在标志物，包括黄嘌呤核苷-5-磷酸和香草基扁桃酸。此外，我们的数据确定了色氨酸和长链酰基肉毒碱水平升高与终末期肾病患者总胆固醇和收缩压降低之间的显著相关性。较高的色氨酸水平也与较高的血清白蛋白水平相关，但这可能反映了色氨酸的显着白蛋白结合。最后，对我们的平台捕获的与24种临床表型相关的尿毒症保留溶质的检查为研究尿毒症毒性机制提供了框架。总之，这些研究利用了在一个充分表征的ESRD队列中获得的代谢组学和代谢表型数据，证明了与普通人群中代谢组学研究的显著差异，并可能为ESRD人群中的新功能途径提供线索。本文的在线版本（doi：10.1186/s12882 - 015 - 0100-y）包含补充材料，可供授权用户使用。
Although metabolomic approaches have begun to document numerous changes that arise in end stage renal disease (ESRD), how these alterations relate to established metabolic phenotypes in uremia is unknown. In 200 incident hemodialysis patients we used partial least squares discriminant analysis to identify which among 166 metabolites could best discriminate individuals with or without diabetes, and across tertiles of body mass index, serum albumin, total cholesterol, and systolic blood pressure. Our data do not recapitulate metabolomic signatures of diabetes and obesity identified among individuals with normal renal function (e.g. elevations in branched chain and aromatic amino acids) and highlight several potential markers of diabetes status specific to ESRD, including xanthosine-5-phosphate and vanillylmandelic acid. Further, our data identify significant associations between elevated tryptophan and long-chain acylcarnitine levels and both decreased total cholesterol and systolic blood pressure in ESRD. Higher tryptophan levels were also associated with higher serum albumin levels, but this may reflect tryptophan’s significant albumin binding. Finally, an examination of the uremic retention solutes captured by our platform in relation to 24 clinical phenotypes provides a framework for investigating mechanisms of uremic toxicity. In sum, these studies leveraging metabolomic and metabolic phenotype data acquired in a well-characterized ESRD cohort demonstrate striking differences from metabolomics studies in the general population, and may provide clues to novel functional pathways in the ESRD population. The online version of this article (doi:10.1186/s12882-015-0100-y) contains supplementary material, which is available to authorized users.
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影响因子：
5.4
作者：
Kalim S;Clish CB;Wenger J;Elmariah S;Yeh RW;Deferio JJ;Pierce K;Deik A;Gerszten RE;Thadhani R;Rhee EP
通讯作者：
Rhee EP
DOI：
10.1056/nejmoa0706130
发表时间：
2008-08-07
期刊：
The New England journal of medicine
影响因子：
--
作者：
Gutiérrez OM;Mannstadt M;Isakova T;Rauh-Hain JA;Tamez H;Shah A;Smith K;Lee H;Thadhani R;Jüppner H;Wolf M
通讯作者：
Wolf M
影响因子：
7.7
作者：
Floegel A;Stefan N;Yu Z;Mühlenbruch K;Drogan D;Joost HG;Fritsche A;Häring HU;Hrabě de Angelis M;Peters A;Roden M;Prehn C;Wang-Sattler R;Illig T;Schulze MB;Adamski J;Boeing H;Pischon T
通讯作者：
Pischon T
影响因子：
37.8
作者：
Cheng S;Rhee EP;Larson MG;Lewis GD;McCabe EL;Shen D;Palma MJ;Roberts LD;Dejam A;Souza AL;Deik AA;Magnusson M;Fox CS;O'Donnell CJ;Vasan RS;Melander O;Clish CB;Gerszten RE;Wang TJ
通讯作者：
Wang TJ
影响因子：
6.1
作者：
Atzler, Dorothee;Schwedhelm, Edzard;Zeller, Tanja
通讯作者：
Zeller, Tanja