Department of Advanced Medicine for Uremia, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Mass Spectrom Rev. 2011 May-Jun;30(3):510-21. doi: 10.1002/mas.20323. Epub 2011 Feb 16.
Mass spectrometry (MS) has been successfully applied for the identification and quantification of uremic toxins and uremia-associated modified proteins. This review focuses on the recent progress in the MS analysis of uremic toxins. Uremic toxins include low-molecular weight solutes, protein-bound low-molecular weight solutes, and middle molecules (peptides and proteins). Based on MS analysis of these uremic toxins, the pathogenesis of the uremic symptoms will be elucidated to prevent and manage the symptoms. Notably, protein-bound uremic toxins such as indoxyl sulfate, p-cresyl sulfate, and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid have emerged as important targets of therapeutic removal. Hemodialysis even with a high-flux membrane cannot efficiently remove the protein-bound uremic toxins because of their high albumin-binding property. The accumulation of these protein-bound uremic toxins in the blood of dialysis patients might play an important role in the development of uremic complications such as cardiovascular disease. Indoxyl sulfate is the most promising protein-bound uremic toxin as a biomarker of progress in chronic kidney disease. Novel dialysis techniques or membranes should be developed to efficiently remove these protein-bound uremic toxins for the prevention and management of uremic complications.
质谱（MS）已成功应用于鉴定和定量尿毒症毒素和尿毒症相关修饰蛋白。本文重点介绍了 MS 分析尿毒症毒素的最新进展。尿毒症毒素包括低分子量溶质、蛋白结合的低分子量溶质和中分子（肽和蛋白）。基于这些尿毒症毒素的 MS 分析，可以阐明尿毒症症状的发病机制，以预防和治疗这些症状。值得注意的是，蛋白结合尿毒症毒素如硫酸吲哚酚、对甲酚硫酸和 3-羧基-4-甲基-5-丙基-2-呋喃丙酸已成为治疗性清除的重要靶点。由于其与白蛋白的高结合特性，即使使用高通量膜进行血液透析也不能有效地清除蛋白结合的尿毒症毒素。这些蛋白结合尿毒症毒素在透析患者血液中的积累可能在心血管疾病等尿毒症并发症的发展中发挥重要作用。硫酸吲哚酚是最有前途的蛋白结合尿毒症毒素，作为慢性肾脏病进展的生物标志物。为了预防和治疗尿毒症并发症，应开发新型透析技术或膜以有效清除这些蛋白结合的尿毒症毒素。
