Patient Oriented Research in Vitamin D Deficiency in CKD

描述(由申请人提供)：玛丽·伦纳德，医学博士，MSCE，儿科学和流行病学副教授，申请续签她的以患者为导向的研究生涯中期奖(K24)。她在导师、领导力和研究效率方面有着出色的记录。在K24奖项的最初四年中，她担任两个已资助和两个未决的K23申请(2011年提交)的主要导师，另一名K23获奖者的联合导师和一名K12儿科科学家发展奖获得者的导师。此外，她还担任了8名医学研究员的MSCE论文委员会主席，为3名获得肾脏生物统计学T32资助的博士生担任论文委员会成员，并指导了6名由研究基金会资助的医学生。她指导了两名初级调查人员成功申请R01，并指导了另外六名K23或K25获奖者进行辅助研究、手稿和拨款申请。她的导师在她的领导下出版了25篇第一作者手稿。K24应用程序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计划，指导以患者为中心的研究(POR)方面的初级研究人员，并开发干预措施，以改善慢性肾脏疾病(CKD)的临床结果。迫切需要改进预防慢性肾脏病的战略。维生素D缺乏可能通过促进炎症和纤维化，加速足细胞损伤和细胞凋亡，直接导致肾脏损害。最初的K24奖的一个主要目标是评估CKD患者的维生素D状况和身体功能。初步结果随后支持了候选人在慢性肾功能不全队列研究(CRIC)中成功申请R01、维生素D缺乏、体能表现和心血管结果。这些数据表明，在第一年，较低的25(OH)维生素D水平与CKD进展的更大风险相关，并记录了CRIC参与者维生素D补充剂使用量的显著增加。这次K24更新的拟议新研究将在CRIC的3939名参与者中确定25(OH)维生素D水平的年度测量与CKD进展之间的联系。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、成纤维细胞生长因子-23和磷水平，捕捉4年内的累积影响，以及评估维生素D结合蛋白的影响，以潜在地改变25(OH)D水平和CKD进展之间的关联。候选人在CRIC正在进行的和拟议的维生素D代谢研究产生的数据，加上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，并培养下一代肾病临床研究人员。

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.