This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Project 1: Cardiac disease in children with chronic renal failure IK23 HL69296-01A1 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 assesment 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 hyperhomocysteinemia 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. Project 2: Cardiovascular abnormalities in children and adolescents with renal transplantation AHA #0160214B Our research is aimed at understanding how cardiovascular disease develops and progresses in children and adolescents with renal transplantation. In particular, we are trying to show that even after successful renal transplantation these patients present with abnormalities of heart structure and function as well as abnormalities of large blood vessels. Recently we showed high frequency of left ventricular hypertrophy (increased size of the left pumping chamber of the heart) in children on chronic dialysis and after transplantation. Since some of the risk factors and mechanisms for the development of heart hypertrophy and blood vessels injury are similar, it is likely that vascular damage such as increased thickness and stiffness of the blood vessel wall are present in children after renal transplantation. We will evaluate cardiovascular structure and function by applying non-invasive methodologies such as rest and stress echocardiography (ultrasound of the heart) as well as high resolution B-mode ultrasound of the blood vessels. We will also evaluate blood pressure using ambulatory blood pressure monitoring, anemia, lipid abnormalities and abnormal blood viscosity as possible risk factors for cardiac or vascular abnormalities. It is hoped that the mechanisms by which cardiovascular disease develops in children and adolescents with renal transplantation will be better understood as a result of this proposal.
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