Cardiac disease in children with chronic renal failure

描述(由申请人提供)： 心血管疾病(CVD)是成人和儿童终末期肾病(ESRD)患者的主要死亡原因。晚期肾功能衰竭的儿童经常会出现心血管改变。在慢性透析治疗开始时，左心室肥厚(LVH)在儿童中已经非常普遍，并在长期透析和肾移植后仍然普遍存在。这些异常在肾功能衰竭过程中首次出现的确切时间尚不清楚。进入慢性透析时LVH已经普遍存在，这一事实有力地表明，在早期慢性肾功能不全(CRI)期间，LV异常发展。我们还假设，除左室肥厚外，CRI儿童患者还会出现左心功能异常和血管异常。该提议背后的假设是，心血管变化发生在相对轻微的CRI儿童中，并随着终末期疾病的临近而进展。为了检验这一概念，我们将评估心脏和血管异常，并确定儿童CRI患者这些异常的危险因素。具体地说，我们将检查：1.通过评估左室质量、左室几何形状来评估心脏结构；2.使用静息和负荷超声心动图来评估左室收缩和舒张期功能；3.通过评估颈动脉内膜-中层厚度(IMT)来检查血管结构；4.通过高分辨率B型超声评估内皮细胞介导的臂动脉血管扩张来评估血管功能。此外，我们将通过动态血压监测、贫血、CRI的病因和进展速度、高脂血症和高同型半胱氨酸血症作为心脏或血管异常的可能危险因素来确定血压的作用，并在初次检查2年后重复评估心血管结构和功能的变化。评价左心室结构、左心功能、颈动脉内膜厚度和内皮功能之间的关系将有助于收集重要信息，为未来CRI儿童心血管疾病的发生发展机制研究提供必要的信息。通过了解这些患者心血管异常发生的危险因素和时间演变，我们可能能够开发和测试预防性干预措施。轻中度CRI可能是识别可改变的危险因素和早期干预可能导致选择性治疗甚至长期预防心脏病的最佳时机。因此，长期目标将是减少在儿童时期发展为慢性肾脏疾病的年轻人的心血管疾病的发生率和流行率。

DESCRIPTION (provided by applicant): 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.