Patient Oriented Research in Vitamin D Deficiency in CKD

描述（由申请人提供）：Mary Leonard，医学博士，MSCE，儿科和流行病学副教授，申请更新她的以患者为导向的研究（K24）中期职业奖。她在指导、领导和研究生产力方面有着出色的记录。在K24奖的最初四年中，她担任了两个已资助和两个未决K23申请（2011年提交）的主要导师，另外一个K23获得者的联合导师和K12儿科科学家发展奖获得者的导师。此外，她还担任了8名内科研究员的MSCE论文委员会主席，3名肾生物统计T32资助的博士生的论文委员会委员，并指导了6名受研究基金会支持的医学学生。她指导两名初级研究人员成功申请R01，并指导另外六名K23或K25研究人员进行辅助研究、撰写论文和申请拨款。在她的带领下，学员发表了25篇第一作者手稿。本次K24申请的总体目标是为候选人提供持续支持，以领导她的多学科研究项目，指导初级研究人员进行面向患者的研究（POR），并开发干预措施以改善慢性肾脏疾病（CKD）的临床结果。迫切需要改进CKD预防策略。维生素D缺乏可能通过促进炎症和纤维化，加速足细胞损伤和凋亡直接导致肾损伤。最初的K24奖励的主要目的是评估CKD中的维生素D状态和身体功能。初步结果随后支持候选药物的R01成功应用，维生素D缺乏，慢性肾功能不全队列研究（CRIC）中的身体表现和心血管结局。这些数据表明，第1年较低的25（OH）维生素D水平与CKD进展的风险增加有关，并且记录了CRIC参与者维生素D补充剂的使用显著增加。这项K24更新的新研究将在CRIC 3939名参与者中确定25（OH）维生素D水平的年度测量与CKD进展之间的关系。创新包括使用病例队列设计（CRIC中的第一个），每年测量25(OH)D， FGF-23和磷水平，以捕获4年间隔内的累积效应，以及评估维生素D结合蛋白的作用，以潜在地改变25(OH)D水平与CKD进展之间的关联。候选人在CRIC中正在进行和拟议的维生素D代谢研究所产生的数据，结合临床流行病学和生物统计中心的资源，将继续提供丰富的机会，吸引新的研究人员到POR，培养下一代肾脏学临床研究人员。

DESCRIPTION (provided by applicant): Mary Leonard, MD, MSCE is an Associate Professor of Pediatrics and Epidemiology applying to renew her Mid-Career Award in Patient Oriented Research (K24). She has an outstanding record of mentorship, leadership and research productivity. During the initial four years of the K24 award, she served as the primary mentor for two funded and two pending K23 applications (submitted 2011), the co-mentor for an additional K23 recipient and the mentor for a K12 Pediatric Scientist Development Award recipient. In addition, she chaired the MSCE thesis committee for 8 physician fellows, served on the thesis committees for 3 PhD students supported by the Renal Biostatistics T32 grant, and mentored 6 medical students supported by research foundations. She mentored two junior investigators in successful R01 applications, and six additional K23 or K25 recipients in ancillary studies, manuscripts and grant applications. Her mentees published 25 first-author manuscripts under her leadership. The overarching goal of this K24 application is to provide the candidate with continued support to lead her multidisciplinary research program, mentor junior investigators in patient oriented research (POR), and develop interventions to improve clinical outcomes in chronic kidney disease (CKD). Improved strategies for the prevention of CKD are urgently needed. Vitamin D deficiency may contribute directly to kidney damage by promoting inflammation and fibrosis, and accelerating podocyte injury and apoptosis. A primary objective of the initial K24 award was to assess vitamin D status and physical function in CKD. The preliminary results subsequently supported the candidate's successful R01 application, Vitamin D Deficiency, Physical Performance and Cardiovascular Outcomes in the Chronic Renal Insufficiency Cohort Study (CRIC). These data suggested that lower 25(OH) vitamin D levels at Year 1 were associated with greater risk of CKD progression, and documented striking increases in vitamin D supplement use by CRIC participants. The proposed New Research in this K24 renewal will identify associations between annual measures of 25(OH) vitamin D levels and progression of CKD within the CRIC cohort of 3939 participants. Innovations include the use of a case-cohort design (the first in CRIC), annual measures of 25(OH)D, FGF-23 and phosphorus levels that will capture cumulative effects over a 4-year interval, and assessment of the effects of vitamin D binding protein to potentially modify the association between 25(OH)D levels and CKD progression. The data generated by the candidate's ongoing and proposed studies of vitamin D metabolism in CRIC, combined with the resources in the Center for Clinical Epidemiology and Biostatistics, will continue to provide a wealth of opportunities to attract new investigators to POR and foster the next generation of clinical investigators in nephrology.