Protein-Bound Toxins-Update 2009
Protein-Bound Toxins-Update 2009
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DOI：
10.1111/j.1525-139x.2009.00576.x
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发表时间：
2009-07-01
影响因子：
1.6
通讯作者：
Brunet, Philippe
中科院分区：
文献类型：
--
作者：
Jourde-Chiche, Noemie;Dou, Laetitia;Brunet, Philippe
蛋白结合的尿毒症保留溶质构成一组，其共同特征是难以通过透析去除。2003年，EUTox小组描述了25种蛋白质结合溶质。它们包括六种晚期糖基化终末产物（AGE）、四种酚类（包括对甲酚）、六种吲哚类（包括硫酸吲哚酚）、两种马尿酸盐、三种多胺和两种肽类（同型半胱氨酸和3-羧基-4-甲基-5-丙基-2-呋喃丙酸（CMPF））。与此同时，三种新化合物被添加到列表中：苯乙酸，二核苷多磷酸和IL-18。在过去的几年中，蛋白结合化合物已被确定为参与慢性肾脏疾病血管病变的一些主要毒素。常规血液透析（HD）对这些溶质的清除率很低，因为只有溶质的游离部分可用于扩散。血液透析滤过增加对流部分可改善净化性能，但对流仅适用于游离部分，其受益有限。改善蛋白质结合溶质的去除的一种可能性是刺激其从结合蛋白解离。这可以在实验中通过将透析液流速和透析器传质面积系数（KoA）设置在比血浆流速高得多的水平，或通过向透析液中添加吸附剂（如活性炭或白蛋白）来获得。在未来，可能会开发出特定的吸附剂。目前，唯一的可能性是使用诸如每日HD和长期HD的方法，这可以使血管外和血管室之间更好地平衡，从而导致更多的蛋白结合化合物的去除。
Protein-bound uremic retention solutes constitute a group whose common characteristic is their difficult removal by dialysis. In 2003, the EUTox group described 25 protein-bound solutes. They comprised six advanced glycation end products (AGE), four phenols (including p-cresol), six indoles (including indoxylsulfate), two hippurates, three polyamines, and two peptides, homocysteine and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF). As then, three new compounds have been added to the list: phenylacetic acid, dinucleoside polyphosphates, and IL-18. During the last years, protein-bound compounds have been identified as some of the main toxins involved in vascular lesions of chronic kidney disease. The removal of these solutes by conventional hemodialysis (HD) is low because only the free fraction of the solute is available for diffusion. The increase in the convective part with hemodiafiltration improves the performance of depuration but convection only applies to the free fraction and its benefit is limited. One possibility to improve the removal of a protein-bound solute would be to stimulate its dissociation from the binding protein. This could be obtained in experiments by setting the dialysate flow rate and the dialyzer mass transfer area coefficient (KoA) at much higher levels than the plasma flow rate, or by adding to the dialysate a sorbent such as activated charcoal or albumin. In the future, specific adsorbents may be developed. Today, the only possibility is to use approaches such as daily HD and long HD which could allow better equilibration between extravascular and vascular compartments and consequently result in greater removal of protein-bound compounds.