Patient Oriented Studies of Vitamin D in Chronic Kidney Disease

维生素 D 在慢性肾脏病中的以患者为导向的研究

• 批准号: 8279507
• 负责人: RAVI THADHANI
• 金额: $ 10.92万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-15 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8279507
• 关键词: Address; Back; Benefits and Risks; Biological; Biological Markers; Biology; Blood specimen; Bone Diseases; Canada; Cardiac; Cardiac Myocytes; Cardiovascular Diseases; Cause of Death; Chronic; Chronic Kidney Failure; Clinical Research; Data Set; Diabetes Mellitus; Diagnosis; Dialysis patients; Dialysis procedure; Disease; Disease Progression; Dose; Educational process of instructing; End stage renal failure; Ergocalciferols; Escherichia coli; Funding; Funding Agency; Gene Expression; Generations; Goals; Grant; Health; Heart Hypertrophy; Hemodialysis; Hormones; Hospitalization; Hypercalcemia; Image; Immune response; Individual; Industry; Infection; Inflammation Mediators; Inflammatory; Institutes; Intervention; Kidney Failure; Laboratories; Lead; Left Ventricular Hypertrophy; Left Ventricular Mass; Link; Measures; Mediating; Mentors; Mentorship; Metabolism; Mid-Career Clinical Scientist Award (K24); Molecular Profiling; Morbidity - disease rate; National Institute of Diabetes and Digestive and Kidney Diseases; Nephrology; New England; Nutritional; Patients; Placebos; Plasma; Population; Population Characteristics; Public Health; Qualifying; Regimen; Research; Research Personnel; Risk Factors; Safety; Scientist; Single Nucleotide Polymorphism; Slice; Staging; Students; Supplementation; Testing; Time; Toxic effect; Training; United States National Institutes of Health; Vitamin D; Vitamin D Analog; Vitamin D Deficiency; Vitamin D3 Receptor; Vitamins; base; capsule; cardiovascular disorder risk; cardiovascular infection; career; cathelicidin; clinically relevant; cohort; coronary artery calcification; cytokine; fibroblast growth factor 23; follow-up; improved; indexing; inorganic phosphate; macrophage; mortality; paricalcitol; patient oriented; patient oriented research; programs; prospective; randomized trial; response; skills; translational study; treatment duration; treatment response

DESCRIPTION (provided by applicant): Vitamin D deficiency is highly prevalent in patients with advanced chronic kidney disease (CKD). Cardiovascular disease (CVD) and infection are the top causes of morbidity and mortality in CKD and end- stage renal disease (ESRD). Evidence generated by the candidate's (Ravi Thadhani, MD, MPH) laboratory has linked CVD progression and altered immune response to inadequate vitamin D levels in CKD/ESRD. Under Dr. Thadhani's direction, a comprehensive patient-oriented research program seeks to investigate the relationship between vitamin D biology and supplementation strategies in terms of mechanistic and clinically relevant endpoints. This application describes three unique aims in three studies (each backed by separate funding sources) that will be pursued by the candidate and his trainees: (1) in DIVINE - an NIH sponsored trial of nutritional vitamin D - his team will determine whether nutritional vitamin D deficiency in ESRD patients leads to altered macrophage function and ex-vivo response to infection; (2) in PRIMO - an industry sponsored trial of active vitamin D and left ventricular hypertrophy [LVH], diastolic function, and cardiac hospitalization in patients with stage 3/4 CKD - his team will determine if baseline levels of 25-hydroxy vitamin D (25D) and fibroblast growth factor-23 (FGF-23) are linked to progression or lack of regression of LVH; and (3) in LUCID - a prospective cohort of incident ESRD subjects supported by the Canadian Institutes of Health - his team will examine whether active vitamin D leads to excess coronary artery calcification. By supporting the candidate's request for this K24 award, important patient-oriented questions will be addressed. Moreover, Dr. Thadhani, with an exemplary record of mentorship, teaching and research, will be afforded the necessary protected time to mentor individuals who comprise a new generation of clinical research fellows and students in Nephrology. PUBLIC HEALTH RELEVANCE: Cardiovascular disease and infection are the primary causes of death in individuals with advanced chronic kidney disease (CKD). Evidence suggests that vitamin D deficiency, which is both highly prevalent and profound in CKD patients, may influence the rate of cardiovascular disease progression and may also mediate immune response to infection in CKD. We have established a comprehensive patient oriented research program that is engaged in testing well-defined hypotheses in patients with late and end-stage renal disease linking vitamin D biology to clinically relevant endpoints. In addition to serving th public health by investigating important patient-oriented questions, this program is a platform for intensive training of clinical research fellows and students by Ravi Thadhani, MD, MPH, whose mentoring efforts will be supported by this K24 award.

描述（由申请人提供）：维生素 D 缺乏症在晚期慢性肾病 (CKD) 患者中非常普遍。心血管疾病（CVD）和感染是 CKD 和终末期肾病（ESRD）发病和死亡的主要原因。候选人（Ravi Thadhani，医学博士、公共卫生硕士）实验室提供的证据表明，CVD 进展和免疫反应改变与 CKD/ESRD 中维生素 D 水平不足有关。在 Thadhani 博士的指导下，一项以患者为导向的综合研究计划旨在从机制和临床相关终点方面研究维生素 D 生物学与补充策略之间的关系。该申请描述了候选人及其学员将追求的三项研究（每项都由单独的资金来源支持）中的三个独特目标：(1) 在 DIVINE 中——NIH 资助的营养维生素 D 试验——他的团队将确定 ESRD 患者营养维生素 D 缺乏是否会导致巨噬细胞功能和对感染的体外反应改变； (2) PRIMO——一项行业赞助的试验，针对 3/4 期 CKD 患者进行活性维生素 D 与左心室肥厚 [LVH]、舒张功能和心脏住院治疗——他的团队将确定 25-羟基维生素 D (25D) 和成纤维细胞生长因子 23 (FGF-23) 的基线水平是否与 LVH 进展或缺乏消退相关； (3) 在 LUCID 中（由加拿大健康研究院支持的 ESRD 事件前瞻性受试者队列），他的团队将检查活性维生素 D 是否会导致冠状动脉过度钙化。通过支持候选人申请 K24 奖项，重要的以患者为导向的问题将得到解决。此外，Thadhani 博士在指导、教学和研究方面有着堪称典范的记录，他将获得必要的受保护时间来指导包括新一代肾病学临床研究员和学生在内的个人。 公共卫生相关性：心血管疾病和感染是晚期慢性肾病 (CKD) 患者死亡的主要原因。有证据表明，维生素 D 缺乏在 CKD 患者中非常普遍且严重，可能会影响心血管疾病的进展速度，也可能介导针对 CKD 感染的免疫反应。我们建立了一个全面的以患者为导向的研究计划，致力于在晚期和终末期肾病患者中测试明确的假设，将维生素 D 生物学与临床相关终点联系起来。除了通过调查以患者为中心的重要问题来服务公共卫生之外，该计划还是一个平台 由医学博士、公共卫生硕士 Ravi Thadhani 对临床研究员和学生进行强化培训，其指导工作将得到 K24 奖项的支持。