VASCULAR ABNORMALITIES IN CRD

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 项目1：慢性肾功能衰竭儿童心脏病IK 23 HL 69296 - 01 A1 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。 晚期肾功能衰竭患儿经常出现心血管变化。 左心室肥大（LVH）在儿童慢性透析治疗开始时已经非常普遍，并且在长期透析期间和肾移植后仍然普遍存在。 确切地说，这些异常在肾衰竭过程中何时首次出现尚不清楚。 LVH在进入慢性透析时已经普遍存在，这一事实强烈表明LV异常在早期慢性肾功能不全（CRI）期间发生。 我们还假设，除了左室肥厚，小儿CRI患者发展的左室功能异常以及血管异常。 该建议的假设是，心血管变化发生在相对轻度CRI的儿童中，并随着终末期疾病的临近而进展。 为了测试这一概念，我们将评估患有CRI的儿科患者的心脏和血管异常，并确定这些异常的风险因素。 具体来说，我们将研究：1。通过评价左心室质量、左心室几何结构评价心脏结构; 2.静息和负荷超声心动图检测左室收缩和舒张功能; 3.通过颈动脉内膜中层厚度（IMT）评估血管结构; 4.高分辨率B型超声评价肱动脉内皮介导的血管舒张功能 此外，我们将通过动态血压监测确定血压的作用，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风险因素，并通过在首次检查后2年重复评价来评估心血管结构和功能的变化。 评价左室结构、左室功能、颈动脉IMT和内皮功能之间的关系，将有助于收集未来CRI儿童心血管疾病发生机制研究所需的重要信息。 通过了解这些患者发生心血管异常的风险因素和时间演变，我们可能能够开发和测试预防性干预措施。轻度至中度CRI可能是识别可改变的风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间。 因此，长期目标将是降低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病率和患病率。 项目2：儿童和青少年肾移植患者的心血管异常AHA #0160214 B 我们的研究旨在了解肾移植儿童和青少年心血管疾病的发展和进展。 特别是，我们试图表明，即使在成功的肾移植后，这些患者仍然存在心脏结构和功能的异常以及大血管的异常。最近，我们发现在长期透析和移植后的儿童中，左心室肥大（心脏左泵血腔的大小增加）的频率很高。 由于心脏肥大和血管损伤的一些风险因素和机制相似，因此肾移植后儿童可能存在血管损伤，如血管壁厚度增加和僵硬。 我们将通过应用非侵入性方法评估心血管结构和功能，如静息和负荷超声心动图（心脏超声）以及血管的高分辨率B型超声。 我们还将使用动态血压监测、贫血、血脂异常和异常血液粘度作为心脏或血管异常的可能风险因素来评估血压。我们希望，通过这项建议，儿童和青少年肾移植后心血管疾病的发展机制将得到更好的理解。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for 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.