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

• 批准号: 9054113
• 负责人: Connie Meeyoung Rhee
• 金额: $ 18.34万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 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/9054113
• 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 heart disease; Data; Databases; Development Plans; Diagnosis; Diagnostic; Diagnostic Imaging; Dialysis patients; Dialysis procedure; Diet; Endocrine; Endocrinology; Environment; Epidemiologic Methods; Epidemiologic Studies; Epidemiologist; Epidemiology; Evaluation; Event; Foundations; Functional disorder; Future; General Population; Goals; Gold; Health; 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; 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; Uremia; Veterans; Vulnerable Populations; Woman; X-Ray Computed Tomography; cardiovascular health; 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; racial disparity; statistics; structural heart disease; wasting

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; 3) 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）：慢性肾脏疾病（CKD）患者（包括透析患者）的甲状腺功能减退症（HT）患病率显著高于非CKD患者。在一般人群中，HT与心血管（CV）发病率和死亡率增加相关，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。CKD患者的CV死亡率极高，其中许多死亡与CHD相关。然而，关于HT对CKD患者CV健康和生存的预后影响知之甚少。 Connie Rhee博士是加州尔湾大学（UCI）的肾病学家，致力于肾脏内学和CKD药物比较有效性领域的研究。她的长期职业目标是成为一名独立的以患者为导向的研究者，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博士能够实现以下目标：1）研究HT及其治疗对CKD患者CHD风险和生存率的影响; 2）在执行以患者为导向的研究方面获得实践经验; 3）在肾脏学，内分泌学，心血管疾病和人类受试者研究方面的创新多学科合作中发展熟练程度; 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，Dr. Rhee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，在该队列中，将使用新型和传统测定法的组合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）之间的相关性，这些终点代表了导致CKD中CHD风险的主要致病机制（目的2）。最后，她将检查HT与死亡率的关联在多大程度上被非透析依赖性CKD患者的基础肾功能所改变，以及这些关联是否通过甲状腺激素治疗得到改善，甲状腺激素治疗使用先进的分析技术（边际结构模型），改善因果推理（目标3）。Rhee博士将有效地利用NIDDK赞助的“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赞助的国家退伍军人事务部（VA）数据库的独特优势，实现这些特定目标。这项拟议研究的结果将有可能揭示HT是CKD中不良CV结局的一种新的、可改变的风险因素;改善这种高度流行的内分泌-肾脏疾病的诊断方法和管理;并减少这一脆弱人群中CV死亡的过度负担。Rhee博士将由她的主要导师Kamyar Kalantar-Zadeh博士密切指导，Kamyar Kalantar-Zadeh博士是UCI肾脏病学教授和主任，他在以患者为导向的研究方面的丰富经验将由Rhee博士的多学科共同导师和合作者团队补充：1）Gregory布伦特博士，大洛杉矶VA医学主席，甲状腺激素研究的著名领导者; 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和主任，在透析患者CV风险因素的纵向评估方面具有专业知识; 3）Steven Brunelli博士，Brigham and Women's Hospital的副流行病学家和DaVita临床研究的高级主任，在因果推断方法方面具有丰富的经验; 4）Csaba Kovesdy博士，孟菲斯退伍军人管理局肾脏病学教授和主任，因其在全国退伍军人群体中的研究而闻名;和5）Matthew Buffett博士，加州大学洛杉矶分校海港心脏计算机断层扫描教授和主任，具有心血管诊断成像方法的专业知识。Rhee博士还将利用UCI的研究环境的财富，其中包括哈罗德西蒙斯肾脏疾病研究和流行病学中心和肾脏病部;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的所在地; UCI的流行病学和统计学部门;以及邻近的加州大学校园的更广泛的研究企业。Rhee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，并为她提供一个 作为一个未来的独立研究者和领导者，在肾内科的坚实基础。