VASCULAR ABNORMALITIES IN CRD

CRD 中的血管异常

• 批准号: 7374489
• 负责人: MARK M. MITSNEFES
• 金额: $ 0.77万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7374489
• 关键词: VASCULAR; ABNORMALITIES; CRD

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.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中出现。列出的机构是中心的机构，不一定是研究者的机构。项目 1：慢性肾功能衰竭儿童的心脏病 IK23 HL69296-01A1 心血管疾病 (CVD) 是成人和儿童终末期肾病 (ESRD) 患者死亡的主要原因。患有晚期肾衰竭的儿童经常出现心血管变化。左心室肥厚 (LVH) 在儿童中在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。这些异常在肾衰竭过程中首次出现的确切时间尚不清楚。事实上，在进入慢性透析时 LVH 已经很普遍，这一事实强烈表明 LV 异常是在早期慢性肾功能不全 (CRI) 期间发生的。我们还假设，除了 LVH 之外，患有 CRI 的儿科患者还会出现 LV 功能异常和血管异常。该提议的假设是，心血管变化发生在 CRI 相对较轻的儿童中，并随着疾病末期的临近而进展。为了检验这个概念，我们将评估 CRI 儿科患者的心脏和血管异常并确定这些异常的危险因素。具体来说，我们将检查： 1. 通过评估左心室质量、左心室几何形状来了解心脏结构； 2. 使用静息和负荷超声心动图检查左室收缩和舒张功能； 3. 通过评估颈动脉内膜中层厚度（IMT）来评估血管结构； 4.通过使用高分辨率B型超声评估内皮介导的肱动脉血管舒张来评估血管功能。此外，我们将通过动态血压监测来确定血压的作用，贫血、病因和 CRI 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，并通过重复评估心血管结构和功能的变化。初次审查后2年进行评估。评估左室结构、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 儿童心血管疾病发展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危险因素和时间演变，我们也许能够开发和测试预防性干预措施。轻度至中度 CRI 可能是最佳时间，在此期间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。因此，长期目标是降低儿童期患有慢性肾病的年轻人心血管疾病的发病率和患病率。 项目 2：肾移植儿童和青少年的心血管异常 AHA #0160214B 我们的研究旨在了解肾移植儿童和青少年心血管疾病如何发生和进展。特别是，我们试图证明，即使在成功进行肾移植后，这些患者也会出现心脏结构和功能异常以及大血管异常。最近，我们发现慢性透析和移植后儿童左心室肥大（心脏左泵室尺寸增大）的频率很高。由于发生心脏肥大和血管损伤的一些危险因素和机制相似，因此肾移植后的儿童可能会出现血管损伤，例如血管壁厚度和硬度增加。我们将通过应用非侵入性方法来评估心血管结构和功能，例如休息和负荷超声心动图（心脏超声）以及高分辨率血管 B 型超声。我们还将使用动态血压监测、贫血、血脂异常和血液粘度异常来评估血压，作为心脏或血管异常的可能危险因素。希望这一提议能够更好地理解接受肾移植的儿童和青少年发生心血管疾病的机制。