Establishing A New Diagnostic Paradigm for Peripheral Artery Disease among Patients with Chronic Kidney Disease

项目摘要 外周动脉疾病（PAD）在慢性肾病（CKD）患者中非常普遍。此外，本发明还提供了一种方法， 与没有CKD的患者相比，PAD的不良后果在CKD患者中更严重。的 PAD的病理生理学和临床表现在CKD患者中可能是独特的。血管 钙化和动脉僵硬在CKD患者中很常见，导致动脉不可压缩， 人工抬高踝臂指数（ABI）。我们先前的研究报告，降低ABI（<1.0）， ABI升高（≥1.4）与PAD相关血运重建和截肢的风险较高相关， 与ABI在1.0至<1.4之间的CKD患者相比， 患者此外，我们的初步研究表明，目前的诊断标准ABI ≤0.9和趾肱动脉 TBI ≤0.7诊断下肢动脉狭窄≥50%的PAD敏感性较差 CKD患者的多普勒超声检查。PAD风险分类模型，包括多种心血管疾病 除了ABI或TBI之外，CVD风险因素显著改善了对患有和 没有PAD。此外，TBI的诊断价值，一种足部灌注的测量，特别是在 在CKD患者中尚未得到很好的评价。的总体目标 拟议的研究是确定更准确的ABI和TBI临界点，用于PAD筛查和诊断， 为CKD患者的PAD筛查和诊断开发一种新方法。具体目标是：（1） 评估当前ABI和TBI诊断标准的准确性，并确定更准确的ABI临界点 PAD的TBI定义为经多普勒超声检查下肢动脉狭窄≥50%;（2）评估 除了ABI或TBI之外，纳入多种CVD风险因素是否会改善歧视， 开发新的PAD筛查和诊断风险分类模型;（3）比较新的切割- PAD与传统临界点（ABI ≤0.9）的ABI点，以及风险分类模型与ABI 在CKD患者中，单独用于预测临床PAD、CVD和全因死亡率的风险。我们将招募420名前- 来自三个慢性肾功能不全队列（CRIC）研究中心的透析CKD患者并进行ABI， 创伤性脑损伤和多普勒超声检查。彩色多普勒超声，将采用多种功能，包括 管腔直径减小，双相波形，收缩期峰值流速比>2.0，以及存在特殊的 广播，将被用作参考标准。CRIC研究招募了约5，500名CKD患者， ABI测量和随访临床结果长达17年。这项研究有99%的统计数据 检测曲线下面积（AUC）为0.70的把握度，零假设AUC值为0.50，2- 单侧显著性水平为0.05（Aim 1），检测AUC比较差异的把握度超过90%（0.85） vs. AUC为0.75（目标2）。拟议的研究可能会改变有关筛选的临床实践， CKD患者PAD的诊断，旨在降低PAD相关的发病率和死亡率。

PROJECT SUMMARY Peripheral artery disease (PAD) is highly prevalent in patients with chronic kidney disease (CKD). In addition, the adverse consequences of PAD are more severe in patients with CKD compared to those without. The pathophysiology and clinical manifestations of PAD might be unique among CKD patients. Vascular calcification and arterial stiffness are common in CKD patients and cause non-compressible arteries and an artificial elevation of ankle brachial index (ABI). Our previous study reported that both reduced ABI (<1.0) and elevated ABI (≥1.4) were associated with a higher risk of PAD-related revascularization and amputation, as well as a higher risk of myocardial infarction, compared to those with an ABI between 1.0 to <1.4 in CKD patients. In addition, our pilot study suggested that the current diagnostic criteria of ABI ≤0.9 and toe-brachial index (TBI) ≤0.7 had poor sensitivity in detecting PAD defined as ≥50% artery stenosis in the lower extremities by Doppler ultrasound among CKD patients. PAD risk classification models including multiple cardiovascular disease (CVD) risk factors in addition to ABI or TBI significantly improved discrimination of those with and without PAD. Furthermore, the diagnostic value of TBI, a measurement of perfusion of the foot, especially in patients with incompressible vessels, has not been well evaluated in CKD patients. The overall objective of the proposed study is to identify more accurate cut-points of ABI and TBI for PAD screening and diagnosis and to develop a novel approach for PAD screening and diagnosis among CKD patients. The specific aims are: (1) to assess the accuracy of current ABI and TBI diagnostic criteria and to identify more accurate cut-points of ABI and TBI for PAD defined as ≥50% artery stenosis in the lower extremities by Doppler ultrasound; (2) to assess whether the inclusion of multiple CVD risk factors in addition to ABI or TBI will improve discrimination and to develop novel risk classification models for PAD screening and diagnosis; and (3) to compare the new cut- points of ABI for PAD vs. the conventional cut-point (ABI ≤0.9), as well as risk classification models vs. ABI alone, in predicting risk of clinical PAD, CVD, and all-cause mortality in CKD patients. We will recruit 420 pre- dialysis CKD patients from three Chronic Renal Insufficiency Cohort (CRIC) study centers and conduct ABI, TBI, and Doppler ultrasound tests. Color Doppler ultrasound, which will employ multiple features including reduction in luminal diameter, monophasic waveform, peak systolic velocity ratio >2.0, and presence of special broadcasting, will be used as the reference standard. The CRIC study recruited about 5,500 CKD patients with ABI measurements and followed clinical outcomes for up to 17 years. The proposed study has 99% statistical power to detect an area under the curve (AUC) of 0.70, with the null hypothesis AUC value of 0.50 and a 2- sided significance level of 0.05 (Aim 1), and over 90% power to detect the difference of comparing AUC of 0.85 vs. AUC of 0.75 (Aim 2). The proposed study may change clinical practice regarding the screening and diagnosis of PAD in CKD patients, with the aim of reducing PAD-related morbidity and mortality.