Metabolite Profiling Identifies Markers of Uremia
Metabolite Profiling Identifies Markers of Uremia
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DOI：
10.1681/asn.2009111132
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发表时间：
2010-06-01
影响因子：
13.6
通讯作者：
Gerszten, Robert E.
中科院分区：
文献类型：
--
作者：
Rhee, Eugene P.;Souza, Amanda;Gerszten, Robert E.
ESRD是一种小分子无序状态。我们应用基于液相色谱/串联质谱仪的代谢物分析技术，对44例终末期肾病患者的血液透析前后和10名年龄匹配的高危空腹对照组的>；350个小分子进行了检测。基线时，尿毒症患者血浆中极性分析物水平升高，脂质分析物水平降低。除了确认许多先前发现的尿毒症毒素的升高外，我们还确定了ESRD的其他几个标志物，包括二元酸(己二酸、丙二酸、甲基丙二酸和马来酸)、生物胺、核苷酸衍生物、酚和神经鞘蛋白。血脂的模式是值得注意的，与对照组相比，较低分子质量的三酰甘油普遍减少，而几个中等分子质量的三酰甘油增加；总甘油三酯的标准测量掩盖了这种异质性。这些观察结果表明，终末期肾病患者甘油三酯分解代谢和/或β-氧化紊乱。正如预期的那样，血液透析过程与大多数极性分析物的显著减少有关。然而，几种代谢物的意外增加表明广泛的分解代谢程序的激活，包括糖酵解、脂解、酮病和核苷酸分解。综上所述，这项研究展示了代谢物图谱在确定终末期肾病标志物方面的应用，为尿毒症血脂异常提供了视角，并拓宽了我们对血液透析的生化效应的理解。
ESRD is a state of small-molecule disarray. We applied liquid chromatography/tandem mass spectrometry-based metabolite profiling to survey >350 small molecules in 44 fasting subjects with ESRD, before and after hemodialysis, and in 10 age-matched, at-risk fasting control subjects. At baseline, increased levels of polar analytes and decreased levels of lipid analytes characterized uremic plasma. In addition to confirming the elevation of numerous previously identified uremic toxins, we identified several additional markers of ESRD, including dicarboxylic acids (adipate, malonate, methylmalonate, and maleate), biogenic amines, nucleotide derivatives, phenols, and sphingomyelins. The pattern of lipids was notable for a universal decrease in lower-molecular-weight triacylglycerols, and an increase in several intermediate-molecular-weight triacylglycerols in ESRD compared with controls; standard measurement of total triglycerides obscured this heterogeneity. These observations suggest disturbed triglyceride catabolism and/or beta-oxidation in ESRD. As expected, the hemodialysis procedure was associated with significant decreases in most polar analytes. Unexpected increases in several metabolites, however, indicated activation of a broad catabolic program, including glycolysis, lipolysis, ketosis, and nucleotide breakdown. In summary, this study demonstrates the application of metabolite profiling to identify markers of ESRD, provide perspective on uremic dyslipidemia, and broaden our understanding of the biochemical effects of hemodialysis.