Wu Chih-Cheng, Hung Szu-Chun, Kuo Ko-Lin, Tarng Der-Cherng
Cardiovascular Center, National Taiwan University Hospital, Hsinchu Branch, Hsinchu 30059, Taiwan.
National Tsing-Hua University, Institute of Biomedical Engineering, Hsinchu 30013, Taiwan.
Toxins (Basel). 2017 Jan 7;9(1):25. doi: 10.3390/toxins9010025.
Patients with chronic kidney disease (CKD) have an increased risk of vascular disease, which is associated with considerable health care costs. Vascular disease in CKD differs clinically and pathobiologically from that in patients with normal renal function. Besides the traditional risk factors, retention of uremic toxins contributes to the pathogenesis of vascular disease in patients with CKD. Indoxyl sulfate is a protein-bound uremic toxin and is inefficiently removed by conventional dialysis. Accumulating evidence suggests that indoxyl sulfate is a vascular toxin involved in atherosclerosis, arteriosclerosis, vascular calcification and vascular repair. Clinically, indoxyl sulfate is associated with total and cardiovascular mortality in patients with CKD. Recent studies have indicated that in addition to coronary and cerebral arteries, indoxyl sulfate plays a role in peripheral artery disease (PAD) and dialysis graft thrombosis. Emerging evidence suggests that indoxyl sulfate is implicated via novel mechanisms, including progenitor cell-related neovascularization and tissue factor-related hypercoagulability. These findings raise the possibility that strategies targeting serum indoxyl sulfate may have the potential to improve the outcomes of PAD and dialysis vascular access in patients with CKD.
慢性肾脏病（CKD）患者发生血管疾病的风险增加，这与可观的医疗费用相关。CKD患者的血管疾病在临床和病理生物学方面与肾功能正常的患者不同。除了传统危险因素外，尿毒症毒素潴留也参与了CKD患者血管疾病的发病机制。硫酸吲哚酚是一种与蛋白结合的尿毒症毒素，常规透析对其清除效率低下。越来越多的证据表明，硫酸吲哚酚是一种血管毒素，参与动脉粥样硬化、动脉硬化、血管钙化和血管修复过程。临床上，硫酸吲哚酚与CKD患者的全因死亡率和心血管死亡率相关。最近的研究表明，除了冠状动脉和脑动脉外，硫酸吲哚酚在周围动脉疾病（PAD）和透析移植物血栓形成中也起作用。新出现的证据表明，硫酸吲哚酚通过新的机制发挥作用，包括与祖细胞相关的新生血管形成和与组织因子相关的高凝状态。这些发现提示，针对血清硫酸吲哚酚的治疗策略可能具有改善CKD患者PAD和透析血管通路结局的潜力。
