Association of diuretics with change in extracellular volume, natriuretic peptides, symptoms, and cardiovascular outcomes in CKD

利尿剂与 CKD 患者细胞外容量、利尿钠肽、症状和心血管结局变化的关系

• 批准号: 9890162
• 负责人: Lucile Parker Gregg
• 金额: --
• 依托单位: VA NORTH TEXAS HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2020-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9890162
• 关键词: Active Learning; Address; Adult; Affect; Aftercare; American; Angiotensin Receptor; Angiotensin-Converting Enzyme Inhibitors; Animal Disease Models; Animals; Antihypertensive Agents; Area; Aspirin; Blood Pressure; Body Weight; Brain natriuretic peptide; Cardiac; Cardiac Output; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Chronic Kidney Failure; Clinical; Clinical Trials; Data; Databases; Diabetes Mellitus; Dialysis procedure; Disease; Disease Progression; Diuretics; Dose; Echocardiography; Ensure; Environmental Wind; Event; Fatigue; Functional disorder; Goals; Healthcare Systems; Heart; Heart failure; Hospitalization; Human; Hypertension; Individual; Informatics; Infrastructure; Intervention; Kidney; Knowledge; Lead; Left Ventricular Mass; Liquid substance; Measurement; Measures; Medical Records; Medical center; Medicine; Mental Depression; Mentors; Mentorship; Modeling; Monitor; Myocardial Infarction; N-terminal; Natriuretic Peptides; Outcome; Outpatients; Painless; Participant; Patient-Focused Outcomes; Patients; Peripheral Resistance; Pharmaceutical Preparations; Physical Examination; Physiology; Plasma; Population; Preventive Intervention; Principal Investigator; Pulse Pressure; Quality of life; Questionnaires; Reporting; Research Design; Research Personnel; Research Project Grants; Retrospective cohort study; Risk; Risk Factors; Scientific Advances and Accomplishments; Spectrum Analysis; Stroke; Symptoms; Texas; Training; Translational Research; Veterans; Visit; blood pressure medication; burden of illness; cardiovascular disorder risk; cardiovascular risk factor; career; career development; common symptom; design; equipment training; extracellular; hemodynamics; high risk; hospitalization rates; improved; indexing; kidney fibrosis; novel; patient oriented; population based; prevent; secondary analysis; standard of care; symposium; targeted treatment; thiazide; tool; translational model

I am a Nephrologist and junior clinical researcher at the VA North Texas Health Care System, an academic VA medical center with over 90 principal investigators and more than 320 research projects. My long- term career goal is to become an independent VA clinical researcher focused on improving cardiovascular (CV) and kidney outcomes in Veterans with chronic kidney disease (CKD). My short-term goals are to conduct crucial initial studies to determine the effects of diuretics on relationships between extracellular volume (ECV) overload, brain natriuretic peptide (BNP) and N-terminal-pro-BNP (NT-pro-BNP), symptoms, CV hemodynamic parameters, and outcomes in Veterans with CKD, and to complete training in conducting a clinical trial, CV and cardiorenal study design, use of bioimpedance spectroscopy (BIS) measurements of ECV, and advanced scientific appraisal. To complete the proposed projects and to ensure that I have the proper training to compete for VA Merit Review, I have designed a comprehensive plan including hands-on mentorship, coursework, conference attendance, and experiential learning to address these specific content areas. I have assembled a diverse team of mentors dedicated to my career development to oversee the scientific and training aims of this proposal. We will use a translational science model to address our central hypothesis, that starting or increasing diuretics in Veterans with CKD is associated with changes in patient-level factors, CV physiology, and population-level outcomes. In the first study, we will determine if initiation of diuretic treatment or increase in dose is associated with changes in BNP and NT-pro-BNP, patient-reported symptom burden, hospitalizations, and short-term hemodynamic parameters in patients with CKD stages 1-3 and elevated blood pressure, and whether these changes correlate with changes in ECV. This clinical trial will include 46 outpatients with CKD stages 1-3 and blood pressure >140/90 mmHg. ECV will be measured by BIS, which is a validated, non-invasive, painless measure of ECV. Plasma BNP and NT-pro-BNP will be measured, and patient-reported fatigue, depression, and quality of life will be quantified using validated questionnaires. Hemodynamic parameters include blood pressure, pulse pressure, total peripheral resistance index, and cardiac index measured by Non- Invasive Cardiac Output Monitoring. A transthoracic echocardiogram will measure left ventricular mass index, valvular disease, and diastolic dysfunction. At the first visit, I will initiate or increase the dose of a thiazide or loop diuretic. Study measures other than echocardiogram will be repeated 4 weeks after the intervention to determine changes in these parameters. We will compare the changes in natriuretic peptides, symptoms, and CV parameters with the change in ECV. Second, we will determine whether initiation of a diuretic vs. non-diuretic is associated with CV and kidney outcomes in patients with CKD stages 1-3 and 4-5 using a large, real-world database of Veterans with CKD. It is considered standard of care that people with CKD should be prescribed an angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) as first-line treatment for high blood pressure. However, many individuals with CKD wind up needing additional anti-hypertensive medications, and the best choice of a second-line agent remains unclear. We will address this question in a retrospective cohort study using the Veterans Affairs Informatics and Computing Infrastructure (VINCI) database. We will identify individuals with CKD who were prescribed an ACEi or ARB as their first blood pressure agent, and then compare CV outcomes between those whose second agent was a diuretic or a non-diuretic. These projects will build on knowledge from animal and human studies of CKD and identify relationships between ECV, natriuretic peptides, symptom burden, and CV disease in patients with CKD, particularly in stages 1-3, in whom preventive interventions may have the greatest impact. The proposed training plan will ensure successful completion of these projects. Ultimately the knowledge gained from these studies will support VA Merit applications to determine whether natriuretic peptides can guide diuretic therapy in patients with CKD.

我是 VA 北德克萨斯医疗保健系统的一名肾脏病学家和初级临床研究员，该系统是 学术 VA 医疗中心拥有 90 多名主要研究人员和 320 多个研究项目。我的长- 学期职业目标是成为一名独立的 VA 临床研究员，专注于改善心血管 (CV) 患有慢性肾病（CKD）的退伍军人的肾脏结局。我的短期目标是进行关键的 初步研究以确定利尿剂对细胞外容量（ECV）超负荷之间关系的影响， 脑钠肽 (BNP) 和 N 末端 BNP 前体 (NT-pro-BNP)、症状、CV 血流动力学 患有 CKD 的退伍军人的参数和结果，并完成临床试验、CV 和 心肾研究设计、使用生物阻抗谱 (BIS) 测量 ECV 以及先进的科学技术 评价。完成拟议的项目并确保我接受适当的培训来竞争 VA 优点评审，我设计了一个全面的计划，包括实践指导、课程作业、会议 出席率和体验式学习来解决这些特定的内容领域。我组建了一支多元化的团队 致力于我职业发展的导师，以监督该提案的科学和培训目标。 我们将使用转化科学模型来解决我们的中心假设，即开始或增加 患有 CKD 的退伍军人使用利尿剂与患者因素、心血管生理学和 人口层面的结果。在第一项研究中，我们将确定是否开始利尿治疗或增加尿量 剂量与 BNP 和 NT-pro-BNP 的变化、患者报告的症状负担、住院治疗、 CKD 1-3 期且血压升高的患者的短期血流动力学参数，以及 这些变化是否与 ECV 的变化相关。该临床试验将包括 46 名 CKD 门诊患者 阶段 1-3 且血压 >140/90 mmHg。 ECV 将由 BIS 进行测量，这是一种经过验证的、非侵入性的、 无痛测量 ECV。将测量血浆 BNP 和 NT-pro-BNP，以及患者报告的疲劳、 抑郁症和生活质量将使用经过验证的问卷进行量化。血流动力学参数 包括血压、脉压、总外周阻力指数、心脏指数等 有创心输出量监测。经胸超声心动图将测量左心室质量指数， 瓣膜疾病和舒张功能障碍。第一次就诊时，我将开始或增加噻嗪类药物的剂量或 袢利尿剂。干预后 4 周将重复超声心动图以外的研究措施，以 确定这些参数的变化。我们将比较利钠肽、症状和 CV 的变化 参数随 ECV 的变化。其次，我们将确定是否开始使用利尿剂与非利尿剂 使用大型真实世界数据与 CKD 1-3 期和 4-5 期患者的 CV 和肾脏结局相关 患有 CKD 的退伍军人数据库。慢性肾病患者应该接受处方药物治疗，这被认为是标准护理 血管紧张素转换酶抑制剂（ACEi）或血管紧张素受体阻滞剂（ARB）作为一线治疗 高血压。然而，许多患有 CKD 的人最终需要额外的抗高血压药物 药物治疗，二线药物的最佳选择仍不清楚。我们将在一个问题中解答这个问题 使用退伍军人事务信息学和计算基础设施 (VINCI) 进行的回顾性队列研究 数据库。我们将确定接受 ACEi 或 ARB 作为首次血压测量的 CKD 患者 剂，然后比较第二种药物为利尿剂或非利尿剂的患者的心血管结果。 这些项目将建立在 CKD 的动物和人类研究知识的基础上，并确定关系 CKD 患者的 ECV、利钠肽、症状负担和 CV 疾病之间的关系，尤其是在不同阶段 1-3，预防性干预措施可能对哪些人产生最大的影响。拟议的培训计划将确保 这些项目的顺利完成。最终从这些研究中获得的知识将支持 VA 确定利钠肽是否可以指导 CKD 患者的利尿治疗的优点应用。