Tanaka Hisae, Sirich Tammy L, Plummer Natalie S, Weaver Daniel S, Meyer Timothy W
The Departments of Medicine, VA Palo Alto HCS and Stanford University, Palo Alto, CA, United States of America.
Bioinformatics Research Group, SRI International, Menlo Park, CA, United States of America.
PLoS One. 2015 Aug 28;10(8):e0135657. doi: 10.1371/journal.pone.0135657. eCollection 2015.
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.
更深入了解肾脏衰竭时蓄积的尿毒症溶质,可能会改善肾脏替代疗法。本研究采用了最大的通用代谢组学平台来识别此类溶质。首先,使用气相色谱和液相色谱与质谱联用的平台,对6名维持性血液透析(HD)患者和6名正常对照者的血浆及血浆超滤液进行了比较。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名结肠完整患者的血浆。我们鉴定出120种溶质为尿毒症溶质,其中48种此前未被报道在肾衰竭时会蓄积。将这48种新鉴定出的溶质与先前报道中鉴定出的溶质相结合,得到了一份超过270种尿毒症溶质的扩展清单。在本研究中鉴定为尿毒症的溶质中,有9种被证明源自结肠,其中6种此前未被鉴定为此类。文献检索显示,许多尿毒症苯和吲哚溶质,包括大多数被证明源自结肠的溶质,都来自植物性食物。其中一些化合物可直接从植物性食物中吸收,其他一些则是由结肠微生物对小肠中未被消化的植物多酚进行代谢产生的。代谢组学方法的一个局限性在于,它低估了使用更定量的检测方法所测得的尿毒症溶质浓度的升高。