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.

我是一名肾病学家，也是退伍军人事务部北德克萨斯医疗保健系统的初级临床研究员 学术退伍军人医学中心拥有90多名主要研究人员和320多个研究项目。我的龙- 任期的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) 以及患有慢性肾脏疾病(CKD)的退伍军人的肾脏结局。我的短期目标是进行至关重要的 初步研究以确定利尿剂对细胞外容量(ECV)超负荷、 脑利钠肽(BNP)和N-末端-BNP原(NT-Pro-BNP)，症状，心血管血流动力学 CKD退伍军人的参数和结果，并完成进行临床试验的培训，CV和 心肾研究设计，使用生物阻抗谱(BIS)测量ECV，以及先进科学 评估。完成建议的项目，并确保我接受适当的培训，以参加退伍军人管理局的竞争 功绩评估，我设计了一个全面的计划，包括亲身实践的指导，课程作业，会议 出席，以及针对这些特定内容领域的体验式学习。我已经组建了一个不同的团队 致力于我的职业发展的导师们监督这项建议的科学和培训目标。 我们将使用翻译科学模型来解决我们的中心假设，即开始或增加 患有CKD的退伍军人服用利尿剂与患者水平因素、心血管生理学和 人口层面的结果。在第一项研究中，我们将确定利尿剂治疗的开始或增加 剂量与BNP和NT-Pro-BNP的变化、患者报告的症状负担、住院时间、 以及CKD 1-3期和血压升高患者的短期血流动力学参数。 这些变化是否与ECV的变化相关。这项临床试验将包括46名慢性肾脏病门诊患者。 1-3期和血压及GT；140/90毫米汞柱。ECV将由BIS测量，BIS是一种经过验证的非侵入性、 无痛量度ECV。将测定血浆BNP和NT-PRO-BNP，患者报告疲劳， 抑郁和生活质量将使用有效的问卷进行量化。血流动力学参数 包括血压、脉压、总外周阻力指数和心脏指数 有创心输出量监测。经胸超声心动图将测量左心室重量指数， 瓣膜疾病和舒张期功能障碍。在第一次就诊时，我会启动或增加噻嗪或 环状利尿剂。除超声心动图以外的研究措施将在干预后4周重复进行，以 确定这些参数中的更改。我们将比较利钠肽、症状和变异系数的变化。 参数随ECV的变化而变化。第二，我们将确定利尿剂和非利尿剂是否开始 与慢性肾脏病1-3期和4-5期患者的心血管和肾脏预后有关 CKD退伍军人数据库。患有慢性肾脏病的人应该被认为是标准的护理 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，许多慢性肾脏病患者最终需要额外的降压药。 药物，以及二线药物的最佳选择仍不清楚。我们将在一个 使用退伍军人事务信息学和计算基础设施(VINCI)的回溯性队列研究 数据库。我们将确定首次血压为ACEI或ARB的CKD患者 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 慢性肾脏病患者ECV、利钠肽、症状负荷与心血管疾病的关系，尤其是分期 1-3，其中预防性干预可能产生最大影响。拟议的培训计划将确保 这些项目圆满完成。最终，从这些研究中获得的知识将支持退伍军人事务部 值得应用来确定利钠肽是否可以指导慢性肾脏病患者的利尿治疗。