An Enlarged Profile of Uremic Solutes.
An Enlarged Profile of Uremic Solutes.
复制标题
DOI：
10.1371/journal.pone.0135657
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Meyer TW
中科院分区：
文献类型：
--
作者：
Tanaka H;Sirich TL;Plummer NS;Weaver DS;Meyer TW
更好地了解肾脏衰竭时积累的尿毒症溶质可能会改善肾脏替代疗法。这项研究采用了最大的广泛使用的代谢组学平台来识别此类溶质。首先使用气相色谱、液相色谱与质谱相结合的平台对 6 名维持性血液透析 (HD) 患者和 6 名正常对照的血浆和血浆超滤液进行比较。进一步的研究比较了 6 名接受全结肠切除术的 HD 患者和 9 名完整结肠的 HD 患者的血浆。我们鉴定出 120 种溶质为尿毒症溶质，其中 48 种溶质此前未曾报道会在肾衰竭中蓄积。将 48 种新鉴定的溶质与之前报告中鉴定的溶质相结合，得出了超过 270 种尿毒症溶质的扩展列表。在当前研究中被鉴定为尿毒症的溶质中，有 9 种被证明是结肠来源的，其中包括 6 种以前未被鉴定为尿毒症的溶质。文献检索显示，许多尿毒症苯基和吲哚溶质，包括大多数来自结肠的溶质，都来自植物性食品。其中一些化合物可以直接从植物性食物中吸收，另一些化合物是由结肠微生物代谢植物多酚产生的，这些多酚在小肠中逃逸消化。代谢组学方法的局限性在于它低估了尿毒症溶质浓度的升高，而尿毒症溶质的浓度是使用更多的定量测定来测量的。
Better knowledge of the uremic solutes that accumulate when the kidneys fail could lead to improved renal replacement therapy. This study employed the largest widely available metabolomic platform to identify such solutes. Plasma and plasma ultrafiltrate from 6 maintenance hemodialysis (HD) patients and 6 normal controls were first compared using a platform combining gas and liquid chromatography with mass spectrometry. Further studies compared plasma from 6 HD patients who had undergone total colectomy and 9 with intact colons. We identified 120 solutes as uremic including 48 that had not been previously reported to accumulate in renal failure. Combination of the 48 newly identified solutes with those identified in previous reports yielded an extended list of more than 270 uremic solutes. Among the solutes identified as uremic in the current study, 9 were shown to be colon-derived, including 6 not previously identified as such. Literature search revealed that many uremic phenyl and indole solutes, including most of those shown to be colon-derived, come from plant foods. Some of these compounds can be absorbed directly from plant foods and others are produced by colon microbial metabolism of plant polyphenols that escape digestion in the small intestine. A limitation of the metabolomic method was that it underestimated the elevation in concentration of uremic solutes which were measured using more quantitative assays.