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

建立慢性肾病患者周围动脉疾病的新诊断范式

基本信息

批准号：
10186101
负责人：
JING CHEN
金额：
$ 65.24万
依托单位：
TULANE UNIVERSITY OF LOUISIANA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-15 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10186101
关键词：
Age Albumins Amputation Angiography Ankle Antidiabetic Drugs Antihypertensive Agents Area Under Curve Arteries Blood Pressure C-reactive protein Caliber Cardiovascular Diseases Chronic Kidney Failure Chronic Kidney Insufficiency Classification Clinical Cohort Studies Color Creatinine Diabetes Mellitus Diagnosis Diagnostic Dialysis procedure Discrimination Doppler Ultrasonography Doppler Ultrasound Ethnic Origin Functional disorder Future General Population Glomerular Filtration Rate Glycosylated hemoglobin A Knowledge Left Lipids Lower Extremity Measurement Measures Modeling Morbidity - disease rate Myocardial Infarction National Institute of Diabetes and Digestive and Kidney Diseases Outcome Patients Perfusion Peripheral arterial disease Pharmaceutical Preparations Pilot Projects Prevalence Race Recording of previous events Reference Standards Reporting Research Risk Risk Factors Sensitivity and Specificity Side Specificity Toes Ultrasonography Urine Vascular calcification Visit adverse outcome alkalinity arterial stiffness artery stenosis cardiovascular disorder risk cigarette smoking clinical center clinical practice clinical risk clinically significant cohort design diagnostic accuracy disorder risk follow-up foot high risk improved indexing inorganic phosphate mortality novel novel diagnostics novel strategies phase 1 study recruit screening sex

项目摘要

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.

项目概要此外，外周动脉疾病（PAD）在慢性肾病（CKD）患者中也很常见。与非 CKD 患者相比，PAD 的不良后果在 CKD 患者中更为严重。 PAD 的病理生理学和临床表现在 CKD 患者中可能是独特的。钙化和动脉僵硬度在 CKD 患者中很常见，会导致动脉不可压缩和我们之前的研究报告称，人工抬高踝臂指数（ABI）可以降低 ABI（<1.0）和 ABI 升高（≥1.4）与 PAD 相关血运重建和截肢风险较高相关，如与 ABI 在 1.0 至 <1.4 之间的 CKD 患者相比，心肌梗塞的风险更高此外，我们的初步研究表明，目前的诊断标准是 ABI ≤0.9 和趾肱。指数（TBI）≤0.7 检测 PAD（定义为下肢动脉狭窄≥50%）的敏感性较差通过多普勒超声对 CKD 患者进行 PAD 风险分类模型，包括多种心血管疾病。除 ABI 或 TBI 之外的疾病（CVD）危险因素显着改善了对患有和此外，TBI（足部灌注的测量）的诊断价值，尤其是在足部。血管不可压缩的患者，在 CKD 患者中尚未得到很好的评估。拟议的研究旨在确定用于 PAD 筛查和诊断的 ABI 和 TBI 的更准确切点，并开发一种针对 CKD 患者进行 PAD 筛查和诊断的新方法，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 切点 PAD 的 TBI 定义为通过多普勒超声检查下肢动脉狭窄≥50% (2) 进行评估；除 ABI 或 TBI 之外纳入多种 CVD 危险因素是否会改善歧视并开发用于 PAD 筛查和诊断的新风险分类模型；(3) 比较新的切割方法 PAD 的 ABI 点与传统切点（ABI ≤0.9）的比较，以及风险分类模型与 ABI 的比较单独预测 CKD 患者的临床 PAD、CVD 和全因死亡率风险时，我们将招募 420 名前期患者。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， TBI 和多普勒超声检查，将采用多种功能，包括管腔直径减小、单相波形、峰值收缩速度比 >2.0 以及存在特殊广播，将作为参考标准 CRIC 研究招募了约 5,500 名 CKD 患者。 ABI 测量和跟踪临床结果长达 17 年。拟议的研究具有 99% 的统计数据。检测曲线下面积 (AUC) 为 0.70 的功效，原假设 AUC 值为 0.50，2- 单侧显着性水平为 0.05（目标 1），检测比较 AUC 0.85 差异的功效超过 90% vs. AUC 为 0.75（目标 2）。拟议的研究可能会改变有关筛查和治疗的临床实践。诊断 CKD 患者的 PAD，旨在降低 PAD 相关的发病率和死亡率。