Jourde-Chiche Noémie, Dou Laetitia, Cerini Claire, Dignat-George Françoise, Brunet Philippe
INSERM U608, UFR Pharmacie, Université Aix-Marseille, Marseille, France.
Semin Dial. 2011 May-Jun;24(3):327-37. doi: 10.1111/j.1525-139X.2011.00925.x.
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.
慢性肾脏病（CKD）患者患心血管疾病的风险比普通人群高得多。参与加速动脉粥样硬化的内皮功能障碍是CKD的一个标志。CKD患者表现出内皮依赖性血管舒张受损、内皮功能障碍的可溶性生物标志物升高以及氧化应激增加。他们还表现出反映内皮损伤（内皮微粒和循环内皮细胞）和修复（内皮祖细胞）的循环内皮细胞群之间的失衡。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。几种尿毒症毒素，大多与蛋白质结合，已被证明具有特定的内皮毒性：不对称二甲基精氨酸（ADMA）、同型半胱氨酸、晚期糖基化终末产物（AGEs），以及最近发现的对甲酚硫酸盐和吲哚硫酸盐。这些毒素在血液透析治疗中均难以清除，它们具有共同的内皮毒性机制：促进促氧化和促炎反应，并抑制内皮修复。本文（i）综述了CKD中内皮功能障碍的证据，（ii）明确了与蛋白质结合的尿毒症毒素在这种功能障碍中的作用，以及（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。
