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

利尿剂与 CKD 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: 10366684
• 负责人: Lucile Parker Gregg
• 金额: --
• 依托单位: MICHAEL E DEBAKEY VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10366684
• 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; Data Set; Databases; Diabetes Mellitus; Dialysis procedure; Disease; Disease Outcome; Disease Progression; Diuretics; Dose; Echocardiography; Effectiveness; End stage renal failure; Ensure; Environmental Wind; Event; Fatigue; Functional disorder; Goals; Heart; Heart failure; Human; Hypertension; Individual; Informatics; Information Systems; Infrastructure; Intervention; Kidney; Knowledge; Lead; Left Ventricular Mass; Link; Liquid substance; Measurement; Measures; Medical Records; Medical center; Medicare/Medicaid; Medicine; Mental Depression; Mentors; Mentorship; Modeling; Monitor; Myocardial Infarction; N-terminal; Natriuretic Peptides; Outcome; Outpatients; Painless; Participant; Patient-Focused Outcomes; Patients; Peripheral Resistance; Persons; Pharmaceutical Preparations; Physical Examination; Physiology; Plasma; Population; Pulse Pressure; Quality of life; Questionnaires; Reporting; Research Design; Research Personnel; Retrospective cohort study; Risk; Risk Factors; Safety; Scientific Advances and Accomplishments; Spectrum Analysis; Stroke; Symptoms; Training; Translational Research; United States; United States Department of Veterans Affairs; Veterans; Visit; blood pressure elevation; blood pressure medication; burden of illness; cardiovascular disorder risk; cardiovascular risk factor; career; career development; common symptom; data warehouse; design; equipment training; extracellular; hemodynamics; high risk; improved; indexing; innovation; kidney fibrosis; novel; patient oriented; population based; prevent; preventive intervention; secondary analysis; standard of care; symposium; targeted treatment; thiazide; tool; translational model

I am a Nephrologist and junior clinical researcher at the Michael E. DeBakey VA Medical Center, an academic VA medical center affiliated with the HSR&D Center for Innovations in Quality, Effectiveness and Safety. 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 initial studies to determine the effects of diuretics on relationships between extracellular volume (ECV), 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 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, 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 Corporate Data Warehouse 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 and identify relationships between ECV, natriuretic peptides, symptom burden, and CV disease in patients with CKD, particularly in stages 1-3, when 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Michael E. Debakey VA医疗中心的肾脏科医生和初级临床研究员 VA学术医学中心隶属于HSR＆D质量，有效性和效率创新中心 安全。我的长期职业目标是成为一名专注于改善的独立VA临床研究人员 患有慢性肾脏病（CKD）的退伍军人的心血管（CV）和肾脏结局。我的短期目标 将进行初步研究，以确定利尿剂对细胞外体积之间关系的影响 （ECV），脑发脂肽（BNP）和N末端Pro-BNP（NT-Pro-BNP），症状，CV血液动力学 参数和CKD退伍军人的结果，并完成进行临床试验的培训，CV 和心脏研究设计，使用ECV的生物阻抗光谱（BIS）测量和先进 科学评估。完成拟议的项目并确保我接受培训以争夺VA 值得评论，我设计了一个全面的计划，包括动手指导，课程，会议 出勤率和经验学习以解决这些特定内容领域。我已经组建了一个多元化的团队 致力于我职业发展的导师，以监督该提议的科学和培训目标。 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 CKD退伍军人的利尿剂与患者水平因素，简历生理学和 人群级别的结果。在第一项研究中，我们将确定利尿治疗的开始或增加 剂量与BNP和NT-Pro-BNP的变化有关，患者报告的症状负担以及短期 CKD阶段1-3和血压升高的患者的血液动力学参数，以及这些是否是否 变化与ECV的变化相关。该临床试验将包括46名CKD阶段1-3和 血压> 140/90 mmHg。 ECV将通过BIS测量，这是经过验证的，无创的，无痛的 ECV的度量。将测量血浆BNP和NT-PRO-BNP，并且患者报告的疲劳，抑郁， 生活质量将使用经过验证的问卷进行量化。血液动力学参数包括血液 压力，脉压，总周围电阻指数和通过非侵入性测量的心脏指数 心输出监测。经胸膜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。在第一次访问中，我将启动或增加噻嗪类或循环的剂量 利尿剂。干预后4周将重复超声心动图以外的研究指标 确定这些参数的变化。我们将比较亚钠肽，症状和 CV参数随ECV的变化。其次，我们将确定利尿剂与非 - 是否开始 利尿剂与CKD阶段1-3和4-5患者的CV和肾脏结局有关 带有CKD的退伍军人的世界数据库。 CKD的人应该是护理标准 开处方的血管紧张素转化酶抑制剂（ACEI）或血管紧张素受体阻滞剂（ARB）首次 高血压的线治疗。但是，许多患有CKD的人需要额外的抗 高血压药物和二线剂的最佳选择尚不清楚。我们将解决这个问题 使用公司数据仓库数据库的回顾性队列研究中的问题。我们将确定 患有CKD的人被处方为ACEI或ARB作为其第一个血压剂，然后 比较第二种药物是利尿剂或非尿液的人之间的简历结果。 这些项目将基于动物和人类研究的知识，并确定关系 CKD患者的ECV，亚位尿肽，症状负担和CV疾病之间，特别是在 第1-3阶段，预防干预措施可能会产生最大的影响。拟议的培训计划将确保 这些项目成功完成。最终，从这些研究中获得的知识将支持VA 确定亚硝醇肽是否可以指导CKD患者的利尿治疗的优点应用。