Hypothyroidism, Cardiovascular Health, and Survival in Kidney Disease

甲状腺功能减退症、心血管健康和肾病患者的生存

基本信息

批准号：
8764492
负责人：
Connie Meeyoung Rhee
金额：
$ 18.58万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-07-01 至 2019-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8764492
关键词：
Address Atherosclerosis Biological Assay Biometry Biostatistical Methods California Cardiac Cardiovascular Diseases Cardiovascular system Cessation of life Chronic Kidney Failure Classification Clinical Clinical Research Clinical Sciences Comorbidity Complement Complication Coronary Arteriosclerosis Coronary heart disease Data Databases Development Plans Diagnosis Diagnostic Diagnostic Imaging Dialysis patients Dialysis procedure Diet Disease Association Endocrine Endocrinology Environment Epidemiologic Methods Epidemiologic Studies Epidemiologist Epidemiology Evaluation Event Foundations Functional disorder Future General Population Goals Gold Health Heart Heart failure Hemodialysis High Prevalence Home environment Hospitals Human Subject Research Hypothyroidism Impaired Renal Function Inflammation Inflammatory Institutes Interdisciplinary Study Kidney Diseases Laboratories Link Los Angeles Malnutrition Measures Medicare Medicine Mentored Patient-Oriented Research Career Development Award Mentors Mentorship Methods Monitor Morbidity - disease rate Multicenter Studies National Institute of Diabetes and Digestive and Kidney Diseases Nephrology Nutritional Outcome P-Selectin Patients Pharmaceutical Preparations Platelet Activation Population Productivity Property Proteins Publishing Relative (related person)Renal function Research Research Design Research Personnel Resources Risk Risk Factors Role Scanning Staging Structural Models Surrogate Endpoint Techniques Therapeutic Index Thrombosis Thyroid Function Tests Thyroid Gland Thyroid Hormones Thyrotropin Thyroxine Time Translational Research Triiodothyronine Universities Veterans Vulnerable Populations Woman X-Ray Computed Tomography cardiovascular risk factor career career development cohort comparative effectiveness coronary artery calcification digital endothelial dysfunction experience follow-up heart disease risk hormone deficiency imaging modality improved innovation insight modifiable risk mortality multidisciplinary novel patient oriented patient oriented research professor prognostic prospective public health relevance statistics

项目摘要

DESCRIPTION (provided by applicant): Patients with chronic kidney disease (CKD), including those on dialysis, have a substantially higher prevalence of hypothyroidism (HT) compared to their non-CKD counterparts. In the general population, HT is associated with increased cardiovascular (CV) morbidity and mortality, presumably due to atherosclerosis, platelet activation and thrombosis, and coronary heart disease (CHD) events. CKD patients have an exceedingly high CV mortality, with many of these fatalities related to CHD. However, little is known about the prognostic implications of HT on the CV health and survival of CKD patients. Dr. Connie Rhee is a nephrologist at the University of California Irvine (UCI) with a strong commitment to the fields of endo-nephrology and drug comparative effectiveness in CKD. Her long-term career goal is to become an independent patient-oriented investigator with a specific focus on thyroid functional disorders in kidney disease. The support of the K23 award will allow Dr. Rhee to achieve the following objectives: 1) investigate the impact of HT and its treatment on CHD risk and survival in CKD patients; 2) gain practical experience in the execution of patient-oriented research; 3) develop proficiency in navigating innovative multidisciplinary collaborations in nephrology, endocrinology, cardiovascular disease, and human subjects research; 4) and acquire expertise in advanced epidemiologic and biostatistical methods. In order to accomplish these objectives, Dr. Rhee will first examine the longitudinal impact of HT on mortality in a well-characterized prospective hemodialysis (HD) cohort in whom thyroid function will be rigorously defined using a combination of novel and traditional assays (Aim 1). She will then examine the association between HT and 3 specific CV surrogate endpoints (endothelial dysfunction, coronary artery calcification, and platelet activation) that represent major pathogenic mechanisms contributing to CHD risk in CKD (Aim 2). Lastly, she will examine the degree to which the association of HT with mortality is modified by underlying renal function in non-dialysis dependent CKD patients, and if these associations are ameliorated by thyroid hormone treatment using advanced analytic techniques (marginal structural modeling) that improve causal inference (Aim 3). Dr. Rhee will efficiently leverage resources from the NIDDK-sponsored "Malnutrition, Diet, and Racial Disparities in CKD" multicenter study and the unique strengths of the NIDDK-sponsored national Veterans Affairs (VA) database as she implements these Specific Aims. Findings from this proposed research will have the potential to uncover HT as a novel, modifiable risk factor for adverse CV outcomes in CKD; improve the diagnostic approach and management of this highly prevalent endocrine-renal disorder; and reduce the excess burden of CV death in this vulnerable population. Dr. Rhee will be closely guided by her primary mentor, Dr. Kamyar Kalantar-Zadeh, Professor and Chief of Nephrology at UCI whose vast experience in patient-oriented research will be complemented by Dr. Rhee's multidisciplinary co-mentor and collaborator team: 1) Dr. Gregory Brent, Professor, Chair of Medicine at the Greater Los Angeles VA, and renowned leader in thyroid hormone research; 2) Dr. Danh Nguyen, Professor and Director of the UCI Biostatistics, Epidemiology, and Research Design Unit with expertise in the longitudinal evaluation of CV risk factors in dialysis patients; ) Dr. Steven Brunelli, Associate Epidemiologist at Brigham and Women's Hospital and Senior Director of DaVita Clinical Research with extensive experience in causal inference methods; 4) Dr. Csaba Kovesdy, Professor and Chief of Nephrology at the Memphis VA widely known for his research in the national veteran population; and 5) Dr. Matthew Budoff, Professor and Director of Cardiac Computed Tomography at Harbor UCLA with expertise in cardiovascular diagnostic imaging methods. Dr. Rhee will also draw upon the wealth of UCI's research environment, which includes the Harold Simmons Center for Kidney Disease Research and Epidemiology and the Division of Nephrology; the Institute of Clinical and Translational Science that is home to the Biostatistics, Epidemiology, and Research Design Unit; UCI's Departments of Epidemiology and Statistics; as well as the broader research enterprise of neighboring University of California campuses. Dr. Rhee's proposed K23 study, mentorship team, career development plan, and collaborative research environment will catalyze her scientific productivity and provide her with a strong foundation as a future independent investigator and leader in endo-nephrology.

描述（由申请人提供）：与非 CKD 患者相比，慢性肾病 (CKD) 患者（包括接受透析的患者）的甲状腺功能减退症 (HT) 患病率要高得多。在一般人群中，HT 与心血管 (CV) 发病率和死亡率增加相关，这可能是由于动脉粥样硬化、血小板活化和血栓形成以及冠心病 (CHD) 事件所致。 CKD 患者的心血管死亡率极高，其中许多死亡与 CHD 相关。然而，人们对 HT 对 CKD 患者的心血管健康和生存的预后影响知之甚少。 Connie Rhee 博士是加州大学欧文分校 (UCI) 的肾脏病专家，致力于肾内病学和 CKD 药物比较疗效领域。她的长期职业目标是成为一名以患者为导向的独立研究者，特别关注肾脏疾病中的甲状腺功能障碍。 K23 奖的支持将使 Rhee 博士实现以下目标：1）研究 HT 及其治疗对 CKD 患者的 CHD 风险和生存的影响； 2）获得执行以患者为中心的研究的实践经验； 3) 提高在肾脏病学、内分泌学、心血管疾病和人类受试者研究领域创新多学科合作的能力； 4）并获得先进的流行病学和生物统计学方法的专业知识。为了实现这些目标，Rhee 博士将首先在一个充分表征的前瞻性血液透析 (HD) 队列中研究 HT 对死亡率的纵向影响，其中将使用新颖和传统测定相结合的方式严格定义甲状腺功能（目标 1））。然后，她将检查 HT 与 3 个特定 CV 替代终点（内皮功能障碍、冠状动脉钙化和血小板活化）之间的关联，这些终点代表导致 CKD 中 CHD 风险的主要致病机制（目标 2）。最后，她将研究非透析依赖性 CKD 患者的基础肾功能对 HT 与死亡率的关联程度的影响，以及这些关联是否可以通过使用先进分析技术（边缘结构模型）的甲状腺激素治疗来改善，从而改善因果推理（目标 3）。在实现这些具体目标时，Rhee 博士将有效利用 NIDDK 资助的“CKD 中的营养不良、饮食和种族差异”多中心研究的资源以及 NIDDK 资助的国家退伍军人事务部 (VA) 数据库的独特优势。这项拟议研究的结果将有可能发现 HT 作为 CKD 不良心血管结局的一种新的、可改变的危险因素；改进这种高度流行的内分泌肾病的诊断方法和管理；并减轻这一弱势群体因心血管死亡造成的额外负担。 Rhee 博士将得到她的主要导师、UCI 肾脏病学教授兼主任 Kamyar Kalantar-Zadeh 博士的密切指导，Rhee 博士的多学科共同导师和合作团队将补充 Kamyar Kalantar-Zadeh 博士在以患者为导向的研究方面的丰富经验：1 ) 格雷戈里·布伦特 (Gregory Brent) 博士，教授、弗吉尼亚州大洛杉矶医学系主任、甲状腺激素研究领域的著名领导者； 2) Danh Nguyen 博士，UCI 生物统计学、流行病学和研究设计部门的教授兼主任，在透析患者心血管危险因素的纵向评估方面拥有专业知识； ) Steven Brunelli 博士，布莱根妇女医院流行病学副学家兼 DaVita 临床研究高级总监，在因果推理方法方面拥有丰富的经验； 4) Csaba Kovesdy 博士，孟菲斯退伍军人管理局肾脏病学教授兼主任，因其对全国退伍军人群体的研究而闻名； 5) Matthew Budoff 博士，加州大学洛杉矶分校 Harbour 心脏计算机断层扫描教授兼主任，拥有心血管诊断成像方法方面的专业知识。 Rhee 博士还将利用 UCI 的研究环境的财富，其中包括 Harold Simmons 肾脏疾病研究和流行病学中心以及肾脏病学部门；临床和转化科学研究所是生物统计学、流行病学和研究设计单位； UCI 的流行病学和统计系；以及邻近的加州大学校园更广泛的研究事业。李博士提出的 K23 研究、导师团队、职业发展计划和协作研究环境将促进她的科学生产力，并为她提供作为未来肾内病学独立研究者和领导者的坚实基础。