Vascular Incompetence in Dialysis Patients-Protein-Bound Uremic Toxins and Endothelial Dysfunction
Vascular Incompetence in Dialysis Patients-Protein-Bound Uremic Toxins and Endothelial Dysfunction
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DOI：
10.1111/j.1525-139x.2011.00925.x
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发表时间：
2011-05-01
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
慢性肾脏病（CKD）患者患心血管疾病的风险比一般人群高得多。参与加速动脉粥样硬化的内皮功能障碍是慢性肾脏病的标志。CKD患者显示内皮依赖性血管舒张功能受损、内皮功能障碍的可溶性生物标志物升高和氧化应激增加。它们还存在反映内皮损伤（内皮微粒和循环内皮细胞）和修复（内皮祖细胞）的循环内皮群体之间的不平衡。尿毒症环境引起的内皮损伤提示尿毒症特异性因素的参与。已证明几种尿毒症毒素（主要与蛋白质结合）具有特定的内皮毒性：ADMA、高半胱氨酸、AGEs，以及最近的对甲苯基硫酸盐和硫酸吲哚酚。这些毒素通过血液透析治疗都很难去除，它们具有共同的内皮毒性机制：它们促进促氧化和促炎反应并抑制内皮修复。这篇文章（i）回顾了CKD内皮功能障碍的证据，（ii）详细说明了蛋白结合尿毒症毒素参与这种功能障碍，（iii）讨论了降低尿毒症毒素浓度或对抗尿毒症毒素对内皮影响的治疗策略。
Patients with chronic kidney disease (CKD) have a much higher risk of cardiovascular diseases than the general population. Endothelial dysfunction, which participates in accelerated atherosclerosis, is a hallmark of CKD. Patients with CKD display impaired endothelium-dependent vasodilatation, elevated soluble biomarkers of endothelial dysfunction, and increased oxidative stress. They also present an imbalance between circulating endothelial populations reflecting endothelial injury (endothelial microparticles and circulating endothelial cells) and repair (endothelial progenitor cells). Endothelial damage induced by a uremic environment suggests an involvement of uremia-specific factors. Several uremic toxins, mostly protein-bound, have been shown to have specific endothelial toxicity: ADMA, homocysteine, AGEs, and more recently, p-cresyl sulfate and indoxyl sulfate. These toxins, all poorly removed by hemodialysis therapies, share mechanisms of endothelial toxicity: they promote pro-oxidant and pro-inflammatory response and inhibit endothelial repair. This article (i) reviews the evidence for endothelial dysfunction in CKD, (ii) specifies the involvement of protein-bound uremic toxins in this dysfunction, and (iii) discusses therapeutic strategies for lowering uremic toxin concentrations or for countering the effects of uremic toxins on the endothelium.