Division of Nephrology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan, ROC.
Atherosclerosis. 2012 Nov;225(1):173-9. doi: 10.1016/j.atherosclerosis.2012.07.012. Epub 2012 Aug 28.
p-Cresyl sulfate (PCS) and indoxyl sulfate (IS) have been reported to predict poor clinical outcomes in hemodialysis (HD) patients. However, little is known about the effect of the two toxins on peripheral arterial disease (PAD) and vascular access dysfunction. Our objective was to explore the association between the two toxins and PAD and vascular access failure (VAF) in a hemodialysis-based cohort.
We enrolled 100 stable and eligible HD patients from a single medical center. These patients were screened for PAD by machine and recorded as ABI (ankle brachial index) and brachial-ankle PWV (pulse wave velocity). Serum levels of PCS, IS and biochemical data were also collected concurrently. In addition, we also recorded the first event of VAF and frequency of PTA and thrombectomy during 3-year follow-up.
Total and free PCS were correlated to right and left ABI and PWV (p < 0.01), and total IS was associated with right and left ABI (p < 0.01) by Pearson's analysis. Repeated measuring by mixed model analysis revealed that serum albumin (p = 0.003), cholesterol (p = 0.01) and total PCS (p = 0.031) had significant correlation with ABI after adjusting other confounding factors. As for brachial-ankle PWV, serum triglyceride (p = 0.002), total IS (p = 0.04) and total PCS (p = 0.050) reached significance finally. In addition, multivariate Cox regression analysis revealed dialysis length and total PCS were related to AV-shunt failure event (Hazard Ratio: 1.14, p = 0.01, and Hazard Ratio: 1.04, p = 0.04, respectively). Both of total and free PCS and IS were also positively linked to numbers of PTA and thrombectomy. Further, the Kaplan-Meier analysis showed only total PCS was significantly associated with vascular access failure event (log rank P = 0.02).
This study shows that the serum levels of PCS and IS were associated with PAD and total PCS could be a valuable determinant of access viability other than traditional or nontraditional risk factors in HD patients.
对甲酚硫酸酯（PCS）和吲哚硫酸酯（IS）已被报道可预测血液透析（HD）患者的不良临床结局。然而，关于这两种毒素对周围动脉疾病（PAD）和血管通路功能障碍的影响知之甚少。我们的目的是在基于血液透析的队列中探讨这两种毒素与 PAD 和血管通路失败（VAF）之间的关系。
我们从一家医疗中心招募了 100 名稳定且符合条件的 HD 患者。这些患者通过机器筛查 PAD，并记录踝肱指数（ABI）和臂踝脉搏波速度（baPWV）。同时收集血清 PCS、IS 水平和生化数据。此外，我们还记录了 3 年随访期间的 VAF 首次事件和 PTA 及血栓切除术的频率。
总 PCS 和游离 PCS 与右、左 ABI 和 PWV 呈正相关（p<0.01），而总 IS 与右、左 ABI 呈正相关（p<0.01），这是通过 Pearson 分析得出的。通过混合模型分析的重复测量发现，血清白蛋白（p=0.003）、胆固醇（p=0.01）和总 PCS（p=0.031）在调整其他混杂因素后与 ABI 显著相关。对于臂踝 PWV，血清甘油三酯（p=0.002）、总 IS（p=0.04）和总 PCS（p=0.050）最终具有统计学意义。此外，多变量 Cox 回归分析显示透析时间和总 PCS 与动静脉分流失败事件相关（危险比：1.14，p=0.01，和危险比：1.04，p=0.04）。总 PCS 和游离 PCS 以及 IS 均与 PTA 和血栓切除术的次数呈正相关。此外，Kaplan-Meier 分析表明只有总 PCS 与血管通路失败事件显著相关（对数秩 P=0.02）。
本研究表明，PCS 和 IS 的血清水平与 PAD 相关，总 PCS 可能是 HD 患者血管通路存活的一个有价值的决定因素，而不仅仅是传统或非传统危险因素。
