Cardiovascular Disease in Children with Chronic Kidney Disease

描述（由申请人提供）：心血管疾病（CVD）是儿童和青少年慢性肾脏疾病（CKD）发病率和死亡率的主要原因。申请人的长期职业目标是通过推进以患者为导向的研究（POR），确定干预措施的生物学靶点，以预防和减缓CKD儿童心血管疾病的进展。自职业生涯早期以来，申请人的研究重点是通过流行病学和转化研究阐明CKD儿童心血管异常的机制。他在这方面的研究一直得到联邦政府的持续资助。他目前正在研究脂联素和其他脂肪因子在CKD儿童心血管异常发展中的作用。Mitsnefes博士也是NIH资助的CKiD研究（U01机制）心血管委员会的联合研究员和联合主席，这是一项旨在研究CKD儿童的多中心努力。K24项目的目的是为候选人提供保护时间和资源，以建立一个全面的项目来研究CKD儿童的心血管疾病。该奖项的具体目标是：1)促进候选人自己的研究；2)指导在儿科肾脏病学中追求POR的初级教师和研究员。第一个目标将基于候选人之前的研究，并将检查维持性透析和肾移植后儿童心肌功能障碍的早期生物标志物：1)左心室心肌周向应变（Ecc）， 2) 31磷磁共振波谱（31P MRS）肌肉能量代谢，3)左心房大小和舒张功能标志物。第二个目标是基于申请人之前的指导经验：自2003年以来，Mitsnefes博士已经指导了8名研究人员，并在17篇同行评议的文章中担任资深作者，他的学员是第一作者。针对早期职业教师和研究人员的指导计划将纳入辛辛那提儿童医院医学中心现有的T32、K12和K30培训计划，以培养杰出的临床科学家，他们将成为独立的研究者。该项目将包括：1)对2名计划申请K23奖项的初级教师进行个性化指导；2)在候选人R01当前研究项目的背景下进行患者导向研究的强化实践培训（2名研究员），以及发展自己的独立研究项目（F32奖）；3)完成辛辛那提大学临床与转化研究研究生项目的理学硕士学位课程；4)参与已建立的其他教学项目，包括手稿和拨款写作、临床试验设计和临床研究方法，以及临床研究中的伦理。辛辛那提儿童医院医学中心为该奖项提供了一个理想的环境，因为它致力于POR，并通过一个强大的临床和转化科学与培训中心不断推动创新临床研究。

DESCRIPTION (provided by applicant): Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in children and young adults with chronic kidney disease (CKD). The applicant's long-term career goal is to define biologic targets for interventions to prevent and slow progression of CVD in children with CKD through advancing Patient-Oriented Research (POR). Since early years of his career, the applicant's research has been focusing on elucidating the mechanisms of cardiovascular abnormalities in children with CKD through epidemiological and translational studies. He has maintained continuous funding at the federal level in this area of research. He currently has an R01 examining the role of adiponectin and other adipokines in the development of cardiovascular abnormalities in children with CKD. Dr. Mitsnefes is also a Co-investigator and a Co-Chair of the Cardiovascular Committee for the NIH funded CKiD study (U01 mechanism), a multicenter effort designed to study children with CKD. The aim of this K24 program is to provide the candidate protected time and resources to build a comprehensive program to study CVD in children with CKD. Specific aims of this award are: 1) further the candidate's own research and 2) mentor junior faculty and fellows who are pursuing POR in pediatric nephrology. The first aim will be based and build upon candidate's previous research and will examine early biological markers of myocardial dysfunction in children on maintenance dialysis and after kidney transplantation: 1) left ventricular myocardial circumferential strain (Ecc), and 2) muscle energy metabolism by 31Phosphorus Magnetic Resonance Spectroscopy (31P MRS), and 3) left atrial size and markers of diastolic function. The second aim is based upon applicant's previous mentoring experience: since 2003 Dr. Mitsnefes has mentored 8 research fellows, and has been senior author on 17 peer-reviewed articles with his mentee as the first author. The Mentoring Plan for early career faculty and research fellows will incorporate the existing T32, K12 and K30 training programs at Cincinnati Children's Hospital Medical Center to produce outstanding clinical scientists who go on to be independent investigators. It will consist of: 1) individualized mentoring of 2 junior faculty who are planning to apply for K23 awards; 2) intensive practical training in patient-oriented research within the context of the current research projects of candidate's R01 for 2 fellows as well as development of their own independent research projects (F32 award); 3) course work in fulfillment of Master's of Science degree in the Graduate Program in Clinical and Translational Research at the University of Cincinnati; 4) participation of fellows in established other didactic programs on manuscript and grant writing, design of clinical trials and clinical research methodology, and ethics in clinical research. Cincinnati Children's Hospital Medical Center provides an ideal setting for this award because of the commitment to POR and ongoing initiatives to promote innovative clinical research through the presence of a strong Center for Clinical and Translational Science and Training. PUBLIC HEALTH RELEVANCE: Cardiovascular disease (CVD) is the major cause of death in children and young adults with chronic kidney disease (CKD). the mechanisms of cardiovascular disease (CVD) in children with chronic kidney disease (CKD). The aim of this K24 program is to provide the candidate protected time and resources to build a comprehensive program to better understand the mechanisms of heart problems in children on dialysis and with kidney transplant. This goal will be achieved by expansion of candidate's own research through using MRI technology to study early heart abnormalities, and by mentoring young investigators who are interested in studying heart problems in children with CKD. By understanding the cause of heart abnormalities, we hope to develop the program for prevention or treatment of this problem in children with CKD.