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是儿科学和流行病学的副教授申请更新她的中期职业生涯奖在面向患者的研究（K24）。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，她担任两个资助和两个待定K23申请（2011年提交）的主要导师，额外的K23收件人的共同导师和K12儿科科学家发展奖获得者的导师。此外，她还主持了8名医生研究员的MSCE论文委员会，在3名由肾脏生物统计学T32资助的博士生的论文委员会任职，并指导了6名由研究基金会支持的医学生。她指导了两名初级研究员成功的R 01申请，以及六名额外的K23或K25受助人的辅助研究，手稿和赠款申请。在她的领导下，她的学员发表了25篇第一作者手稿。该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，指导以患者为导向的研究（POR）的初级研究人员，并制定干预措施以改善慢性肾脏病（CKD）的临床结局。因此，迫切需要改善CKD的预防策略。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而直接导致肾损伤。最初K24奖项的主要目的是评估CKD患者的维生素D状态和身体功能。初步结果随后支持候选人在慢性肾功能不全队列研究（CRIC）中成功申请R 01、维生素D缺乏、体能和心血管结局。这些数据表明，第1年较低的25（OH）维生素D水平与CKD进展的风险较高相关，并记录了CRIC参与者使用维生素D补充剂的显着增加。本次K24更新中拟议的新研究将在3939名参与者的CRIC队列中确定25（OH）维生素D水平的年度测量值与CKD进展之间的关联。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年间隔的累积效应，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学中心的资源，将继续提供大量机会，吸引新的研究人员加入POR，并培养下一代肾脏病学临床研究人员。

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.