New Uremic Toxins - Which Solutes Should Be Removed?
New Uremic Toxins - Which Solutes Should Be Removed?
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DOI：
10.1159/000321750
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发表时间：
2011-01-01
期刊：
影响因子：
--
通讯作者：
Vanholder, Raymond
中科院分区：
文献类型：
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作者：
Glorieux, Griet;Vanholder, Raymond
慢性肾病 (CKD) 的特点是多种化合物逐渐滞留，其中几种化合物在心血管损伤中发挥作用，而心血管损伤是 CKD 死亡的主要原因。在过去的几年中，特别是蛋白质结合化合物（例如硫酸吲哚酚和对甲酚硫酸盐）和/或中间分子（例如AGE、细胞因子和二核苷多磷酸）已被确定为涉及血管病变的一些主要毒素，影响CKD中的内皮细胞、白细胞、血小板和/或血管平滑肌细胞功能。然而，许多这些溶质很难通过标准透析策略去除。蛋白质结合溶质的去除仍然受到限制，因为只有溶质的游离部分可用于（主要是扩散）去除，而较大的中间分子（主要是较大的肽化合物）的去除可以通过增加透析器孔径和应用对流策略来实现。此外，还探索了寻求特异性去除（例如通过吸附）和/或药理学中和相关化合物的分子影响的新治疗策略，旨在改善 CKD 患者的预后。版权所有 (C) 2011 S. Karger AG，巴塞尔
Chronic kidney disease (CKD) is characterized by the progressive retention of a myriad of compounds, several of which play a role in cardiovascular damage, a major cause of mortality in CKD. Over the past years, especially protein-bound compounds (e.g. indoxylsulfate and p-cresylsulfate) and/or middle molecules (e.g. AGEs, cytokines and dinucleoside polyphosphates) have been identified as some of the main toxins involved in vascular lesions affecting endothelial cell, leukocyte, platelet and/or vascular smooth muscle cell function in CKD. Many of these solutes, however, are difficult to remove by standard dialysis strategies. The removal of protein-bound solutes remains limited because only the free fraction of the solute is available for, mostly diffusive, removal, while removal of the larger middle molecules (mostly larger peptidic compounds) can be obtained by increasing dialyzer pore size and by applying convective strategies. In addition, new therapeutic strategies pursuing specific removal (e.g. by adsorption) and/or pharmacological neutralization of the molecular impact of the responsible compounds are explored, aiming at an improved outcome in CKD patients. Copyright (C) 2011 S. Karger AG, Basel