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

项目总结 外周动脉疾病(PAD)在慢性肾脏病(CKD)患者中非常常见。此外, 与无PAD的患者相比，CKD患者PAD的不良后果更为严重。这个 PAD的病理生理和临床表现在CKD患者中可能是独一无二的。血管 钙化和动脉僵硬在CKD患者中很常见，并导致不可压缩的动脉和 人工抬高踝臂指数(ABI)。我们之前的研究报告说，ABI(&lt；1.0)和 ABI升高(≥1.4)与PAD相关的血管重建和截肢的风险更高，因为 与CKD中ABI在1.0至1.4之间的患者相比，CKD患者发生心肌梗死的风险更高 病人。此外，我们的初步研究表明，目前ABI≤0.9%和趾臂的诊断标准 指数(≤)0.7时PAD的敏感性较差，PAD定义为≥50%的下肢动脉狭窄 对CKD患者进行了多普勒超声检查。包括多个心血管疾病的PAD风险分类模型 除ABI或TBI外，疾病(CVD)风险因素显著改善了患有和 不带垫子。此外，脑损伤的诊断价值，一种测量足部血流灌注，特别是在 有不可压缩血管的患者，在CKD患者中尚未得到很好的评估。《公约》的总体目标 建议的研究是确定更准确的ABI和TBI的切入点，用于PAD筛查和诊断，并 开发一种新的方法用于慢性肾脏病患者的PAD筛查和诊断。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切入点 超声心动图诊断为≥50%的下肢动脉狭窄；(2) 除了ABI或TBI之外，纳入多种心血管疾病风险因素是否会改善歧视和 开发用于PAD筛查和诊断的新的风险分类模型；以及(3)比较新的CUT- PAD的资产负债指数与传统切入点(资产负债指数≤0.9)的比较，以及风险分类模型与资产负债指数的比较 单独预测CKD患者的临床PAD、心血管疾病和全因死亡的风险。我们将招募420名预科医生 来自三个慢性肾功能不全(CRIC)研究中心的透析CKD患者并进行ABI， 和多普勒超声检查。彩色多普勒超声将采用多种功能，包括 管腔内径减小，单相波形，收缩峰值速度比<2.0，并存在特殊的 广播，将作为参考标准。CRIC研究招募了大约5500名患有CKD的患者 ABI测量和跟踪临床结果长达17年。拟议的研究有99%的统计数据 检测曲线下面积的功率(AUC)为0.70，零假设AUC值为0.50，2- 单侧显著性水平0.05(目标1)，90%以上检验比较AUC差异0.85 AUC为0.75(目标2)。拟议的研究可能会改变有关筛查和 诊断CKD患者的PAD，目的是减少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.