Supplementary Material for: Vascular Calcification Markers and Hemodialysis Vascular Access Complications

<b><i>Background:</i></b> Arteriovenous (AV) access dysfunction is a common complication in hemodialysis patients. Markers of vascular calcification are associated with cardiovascular outcomes and mortality in this population, but their association with vascular access outcomes is unknown. In this study, we aimed to evaluate the association between selected vascular calcification makers and vascular access complications in a cohort of hemodialysis patients. <b><i>Method:</i></b> Fetuin-A, osteopontin (OPN), osteoprotegerin (OPG), and bone morphogenetic protein-7 (BMP-7) were measured in blood samples from 219 dialysis patients in the Choice for Healthy Outcomes in Caring for end-stage renal disease study; these patients were using a permanent vascular access. Participants were followed for up to 1 year or until the occurrence of a vascular access intervention or replacement. Associations with AV fistula (AVF) and AV graft (AVG) intervention-free survival were assessed in models adjusted for demographic characteristics, comorbidities, and inflammation. <b><i>Results:</i></b> A total of 24 out 103 participants with an AVF and 43 out of 116 participants with an AVG had an intervention during follow-up. Lower fetuin-A, higher OPN, and higher BMP-7 were associated with a higher risk of AVF intervention (adjusted hazard ratios [aHR] for highest versus lowest tertile = 0.30 [95% CI 0.10–0.94]) for fetuin-A, 3.84 (95% CI 1.16–12.74) for OPN, and 3.49 (95% CI 1.16–10.52) for BMP-7. OPG was not significantly associated with the risk of AVF intervention. The associations of OPN and BMP-7 with AVF intervention appeared stronger among participants without diabetes (aHR 8.06; 95% CI 1.11–58.57 for OPN and aHR 2.55; 95% CI 1.08–6.08 for BMP-7, respectively) than among their counterparts with diabetes (<i>p</i> interaction = 0.06). None of the markers studied were significantly associated with AVG interventions. <b><i>Conclusion:</i></b> Lower fetuin-A and higher OPN and BMP-7 are associated with complications in AVF but not in AVG, suggesting a role for calcification in the pathogenesis AVF failure.

<b><i>背景：</i></b> 动静脉（arteriovenous, AV）通路功能障碍是血液透析患者的常见并发症。血管钙化标志物与该人群的心血管结局及死亡率存在关联，但此类标志物与血管通路结局的关联尚未明确。本研究旨在评估终末期肾病照护健康结局选择（Choice for Healthy Outcomes in Caring for End-Stage Renal Disease, 简称CHOICE）队列中，选定的血管钙化标志物与血液透析患者血管通路并发症的关联。<b><i>方法：</i></b> 研究纳入该队列中219名采用永久性血管通路的透析患者，采集其血液样本检测胎球蛋白-A（fetuin-A）、骨桥蛋白（osteopontin, OPN）、骨保护素（osteoprotegerin, OPG）及骨形态发生蛋白-7（bone morphogenetic protein-7, BMP-7）水平。对所有参与者开展最长1年的随访，直至其发生血管通路干预或置换事件。通过校正人口学特征、合并症及炎症状态的统计模型，评估上述标志物与动静脉内瘘（arteriovenous fistula, AVF）和人工血管动静脉移植物（arteriovenous graft, AVG）无干预生存情况的关联。<b><i>结果：</i></b> 随访期间，103名动静脉内瘘患者中有24名接受了血管通路干预，116名人工血管动静脉移植物患者中有43名接受了通路干预。较低的胎球蛋白-A水平、较高的骨桥蛋白水平及较高的骨形态发生蛋白-7水平与动静脉内瘘干预风险升高显著相关：胎球蛋白-A最高三分位组相较最低三分位组的校正后风险比（adjusted hazard ratios, aHR）为0.30（95%置信区间[CI] 0.10–0.94），骨桥蛋白为3.84（95%CI 1.16–12.74），骨形态发生蛋白-7为3.49（95%CI 1.16–10.52）。骨保护素与动静脉内瘘干预风险无显著关联。在无糖尿病的参与者中，骨桥蛋白和骨形态发生蛋白-7与动静脉内瘘干预的关联强度高于糖尿病参与者（骨桥蛋白的校正后风险比为8.06；95%CI 1.11–58.57，骨形态发生蛋白-7为2.55；95%CI 1.08–6.08，交互作用p值=0.06）。本研究所检测的所有标志物均与人工血管动静脉移植物干预风险无显著关联。<b><i>结论：</i></b> 较低的胎球蛋白-A水平、较高的骨桥蛋白及骨形态发生蛋白-7水平与动静脉内瘘并发症相关，但与人工血管动静脉移植物并发症无关，提示血管钙化在动静脉内瘘失效的发病机制中发挥一定作用。