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）：与非CKD对应物相比，甲状腺功能减退症（HT）患者的患病率要高得多。在普通人群中，HT与心血管（CV）发病率和死亡率的增加有关，大概是由于动脉粥样硬化，血小板激活和血栓形成以及冠状动脉疾病（CHD）事件。 CKD患者的CV死亡率极高，其中许多死亡与CHD有关。然而，关于HT对CKD患者的CV健康和存活的预后意义知之甚少。 Connie Rhee博士是加利福尼亚大学尔湾分校（UCI）的肾脏科医生，对CKD中的肾脏否和药物比较有效性领域有着坚定的承诺。她的长期职业目标是成为一名独立的面向患者的研究者，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及其对CKD患者冠心病风险和生存的影响； 2）在执行面向患者的研究方面获得实践经验； 3）培养肾脏学，内分泌学，心血管疾病和人类受试者研究的创新多学科合作的熟练程度； 4）并获得高级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博士将首先检查HT对特征良好的前瞻性血液透析（HD）队列中死亡率的纵向影响，其中甲状腺功能将使用新颖的分析和传统分析的组合进行严格定义（AIM 1）。然后，她将检查HT和3个特定的CV替代终点（内皮功能障碍，冠状动脉钙化和血小板激活）之间的关联，这些终点代表了有助于CKD中CHD风险的主要致病机制（AIM 2）。最后，她将检查HT与死亡率的关联通过非透析依赖性CKD患者的肾功能来改变的程度，以及是否使用先进的分析技术（边际结构模型）通过甲状腺激素治疗来改善这些关联，以改善因果关系（AIM 3）。 Rhee博士将有效利用NIDDK赞助的“ CKD中的营养不良，饮食和种族差异”多中心研究，以及NIDDK赞助的国家退伍军人事务（VA）数据库的独特优势，因为她实现了这些特定的目标。这项拟议的研究的结果将有可能发现HT是CKD中不良CV结果的新型，可修改的风险因素。改善这种高度普遍的内分泌肾脏疾病的诊断方法和管理；并减轻该脆弱人群中简历死亡的多余负担。 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）UCI生物统计学，流行病学和研究设计部门教授兼主任Danh Nguyen博士在透析患者的简历危险因素方面具有专业知识； 3）Brigham和妇女医院副流行病学家，Davita临床研究高级主任Steven Brunelli博士，在因果推理方法方面具有丰富的经验； 4）孟菲斯VA教授兼肾脏学首席Csaba Kovesdy博士以其在国家退伍军人人口中的研究而闻名； 5）Harbour UCLA的心脏计算机断层扫描教授兼主任Matthew Budoff博士，具有心血管诊断成像方法的专业知识。 Rhee博士还将借鉴UCI研究环境的财富，其中包括Harold Simmons肾脏疾病研究与流行病学中心和肾脏科学系；临床与转化科学研究所，是生物统计学，流行病学和研究设计部门的所在地； UCI的流行病学和统计部门；以及邻国加利福尼亚大学校园的更广泛的研究企业。 Rhee博士提议的K23研究，指导团队，职业发展计划和协作研究环境将催化她的科学生产力，并为她提供 作为未来独立研究者和内部杀伤力领导者的强大基础。