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 i s 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.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Midcareer Investigator Award in Patient-Oriented Research (K24)
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Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
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Rankin, Tracy L
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Cincinnati Children's Hospital Medical Center
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Hamdani, Gilad; Nehus, Edward J; Hanevold, Coral D et al. (2017) Ambulatory Blood Pressure, Left Ventricular Hypertrophy, and Allograft Function in Children and Young Adults After Kidney Transplantation. Transplantation 101:150-156
Laskin, Benjamin L; Huang, Guixia; King, Eileen et al. (2017) Short, frequent, 5-days-per-week, in-center hemodialysis versus 3-days-per week treatment: a randomized crossover pilot trial through the Midwest Pediatric Nephrology Consortium. Pediatr Nephrol 32:1423-1432
Ku, Elaine; Kopple, Joel D; McCulloch, Charles E et al. (2017) Associations Between Weight Loss, Kidney Function Decline, and Risk of ESRD in the Chronic Kidney Disease in Children (CKiD) Cohort Study. Am J Kidney Dis :
VanDeVoorde 3rd, Rene G; Mitsnefes, Mark M (2016) Hypertension in chronic kidney disease: role of ambulatory blood pressure monitoring. Prog Pediatr Cardiol 41:67-73
Mitsnefes, Mark M; Pierce, Chris; Flynn, Joseph et al. (2016) Can office blood pressure readings predict masked hypertension? Pediatr Nephrol 31:163-6
Laskin, Benjamin L; Mitsnefes, Mark M; Dahhou, Mourad et al. (2015) The mortality risk with graft function has decreased among children receiving a first kidney transplant in the United States. Kidney Int 87:575-83
Xiao, Nianzhou; Devarajan, Prasad; Inge, Thomas H et al. (2015) Subclinical kidney injury before and 1 year after bariatric surgery among adolescents with severe obesity. Obesity (Silver Spring) 23:1234-8
Paoli, Sara; Mitsnefes, Mark M (2014) Coronary artery calcification and cardiovascular disease in children with chronic kidney disease. Curr Opin Pediatr 26:193-7
Nehus, Edward; Furth, Susan; Warady, Bradley et al. (2014) Correlates of leptin in children with chronic kidney disease. J Pediatr 165:825-9
Xiao, Nianzhou; Jenkins, Todd M; Nehus, Edward et al. (2014) Kidney function in severely obese adolescents undergoing bariatric surgery. Obesity (Silver Spring) 22:2319-25

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