Cardiovascular disease (CVD) is the leading cause of death in adult and pediatric patients with end-stage renal disease (ESRD). Cardiovascular changes are frequently present in children with advanced renal failure. Left ventricular hypertrophy (LVH) is already highly prevalent in children at the initiation of chronic dialysis therapy, and remains prevalent during long-term dialysis and after renal transplantation. Exactly when these abnormalities first appear in the course of renal failure is not known. The fact that LVH is already prevalent at the time of entry to chronic dialysis strongly indicates that LV abnormalities develop during early chronic renal insufficiency (CRI). We also postulate that in addition to LVH, pediatric patients with CRI develop abnormalities of LV function as well as vascular abnormalities. The hypothesis underlying the proposal is that cardiovascular changes occur in children with relatively mild CRI, and progress as end-stage disease approaches. To test this concept, we will assess cardiac and vascular abnormalities and identify risk factors for these abnormalities in pediatric patients with CRI. Specifically, we will examine: 1. Cardiac structure by evaluation of LV mass, LV geometry; 2. LV systolic and diastolic function using rest and stress echocardiography; 3. Vascular structure by assessment of carotid artery intima-media thickness (IMT); 4. Vascular function by assessment of endothelium-mediated vasodilatation of the brachial artery using high-resolution B-mode ultrasound. In addition, we will determine the role of blood pressure by ambulatory blood pressure monitoring, anemia, etiology and rate of progression of CRI, hyperlipidemia and hyper-homocysteinemia as possible risk factors for cardiac or vascular abnormalities and assess the changes of cardiovascular structure and function by repeating the evaluation 2 years after initial examination. Evaluation of the relationships between LV structure, LV function, carotid IMT and endothelial function will help to gather the important information needed for future mechanistic studies of development of cardiovascular disease in children with CRI. By understanding the risk factors and temporal evolution by which cardiovascular abnormalities develop in these patients, we may then be able to develop and test preventive interventions. It is possible that mild-to-moderate CRI is the optimal time during which identification of modifiable risk factors and early intervention might lead to elective treatment and even to prevention of cardiac disease over the long term. Thus, the long-term goal will be to decrease the incidence and prevalence of cardiovascular disease in young adults who developed chronic renal disease during childhood.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
Application #
Study Section
Special Emphasis Panel (ZHL1-CSR-F (M3))
Program Officer
Scott, Jane
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Children's Hospital Med Ctr (Cincinnati)
United States
Zip Code
Weaver Jr, Donald J; Kimball, Thomas R; Koury, Phillip R et al. (2009) Cardiac output and associated left ventricular hypertrophy in pediatric chronic kidney disease. Pediatr Nephrol 24:565-70
Wilson, Amy C; Mitsnefes, Mark M (2009) Cardiovascular disease in CKD in children: update on risk factors, risk assessment, and management. Am J Kidney Dis 54:345-60
Weaver Jr, Donald J; Kimball, Thomas; Witt, Sandra A et al. (2008) Subclinical systolic dysfunction in pediatric patients with chronic kidney disease. J Pediatr 153:565-9
Weaver Jr, Donald J; Kimball, Thomas R; Knilans, Timothy et al. (2008) Decreased maximal aerobic capacity in pediatric chronic kidney disease. J Am Soc Nephrol 19:624-30
Mitsnefes, Mark M; Kathman, Thelma S; Mishra, Jaya et al. (2007) Serum neutrophil gelatinase-associated lipocalin as a marker of renal function in children with chronic kidney disease. Pediatr Nephrol 22:101-8
Mitsnefes, Mark; Kartal, Janis; Khoury, Philip et al. (2007) Adiponectin in children with chronic kidney disease: role of adiposity and kidney dysfunction. Clin J Am Soc Nephrol 2:46-50
Mitsnefes, Mark; Kimbal, Thomas; Kartal, Janis et al. (2006) Serum cystatin C and left ventricular diastolic dysfunction in children with chronic kidney disease. Pediatr Nephrol 21:1293-8
Mitsnefes, Mark M; Kimball, Thomas R; Kartal, Janis et al. (2006) Progression of left ventricular hypertrophy in children with early chronic kidney disease: 2-year follow-up study. J Pediatr 149:671-5
Mitsnefes, Mark M; Kimball, Thomas R; Kartal, Janis et al. (2005) Cardiac and vascular adaptation in pediatric patients with chronic kidney disease: role of calcium-phosphorus metabolism. J Am Soc Nephrol 16:2796-803
Mitsnefes, Mark M; Kimball, Thomas R; Witt, Sandra A et al. (2004) Abnormal carotid artery structure and function in children and adolescents with successful renal transplantation. Circulation 110:97-101

Showing the most recent 10 out of 13 publications