HIV-Related Proteinuria and Endothelial Dysfunction

HIV 相关蛋白尿和内皮功能障碍

基本信息

批准号：
7242558
负责人：
SAMIR KUMAR GUPTA
金额：
$ 12.47万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-07-15 至 2008-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7242558
关键词：
AIDS clinical trial group AIDS-Associated Nephropathy AIDS/HIV problem Academic Medical Centers Address Angiotensin-Converting Enzyme Inhibitors Anti-Retroviral Agents Archives Blood Pressure Cardiovascular Diseases Cardiovascular system Caring Class Clinical Investigator Clinical Pathology Clinical Research Clinical Trials Design Cohort Studies Collaborations Communicable Diseases Data Detection Development Diabetes Mellitus Disease Early identification Endocrinology Environment Evaluation Studies Event Excretory function Fibrinogen Fostering Functional disorder Future General Population Glucose Goals HIV HIV Seropositivity High Prevalence Highly Active Antiretroviral Therapy Homeostasis Indiana Insulin Intervention Kidney Kidney Diseases Knowledge Life Style Link Lipids Measurement Measures Mediating Medical Mentors Metabolic Microalbuminuria Non-Insulin-Dependent Diabetes Mellitus Patients Personal Satisfaction Persons Physiological Population Positioning Attribute Prevalence Prevention Principal Investigator Protease Inhibitor Proteins Proteinuria RNA-Directed DNA Polymerase Range Renal glomerular disease Reporting Research Research Personnel Research Training Sampling Screening procedure Shapes Therapeutic Therapy Clinical Trials Training Treatment Protocols Ultrasonography Universities Urine Vascular Endothelium Vasomotor Work base brachial artery career experience glomerular function kidney vascular structure member mortality non-nucleoside reverse transcriptase inhibitors programs prospective

项目摘要

DESCRIPTION (provided by applicant): Renal and cardiovascular diseases in HIV-infected patients are increasingly reported and may be interrelated. Total proteinuria, a widely used initial screening marker for renal disease, is extremely common in HIV-infected patients. In the general population, proteinuria is also associated with systemic endothelial dysfunction, a predictor of future cardiovascular events. Therefore, we hypothesize that endothelial dysfunction may be associated with the high prevalence of proteinuria in the HIV-infected population. Furthermore, because protease inhibitors are associated with endothelial dysfunction, we hypothesize that this class of antiretrovirals may specifically result in glomerular endothelial disease, manifested initially as microalbuminuria. The specific aims of this study are to (1) determine the relationships between proteinuria and systemic endothelial dysfunction in HIV-infected patients and (2) determine the effects of protease inhibitor-based HAART on microalbuminuria in HIV-infected patients. To address Aim #1, we propose to perform a prospective, cohort study of HIV-infected subjects cared for at the Indiana University Medical Center. Specifically, ultrasound-measured flow mediated dilation of the brachial artery (a physiologic measurement of endothelial function), lipids, insulin and glucose levels, anthropometrics, lifestyle factors, and blood pressures of two HIV-infected groups (those with persistent proteinuria vs. those without proteinuria) will be compared at baseline and again in two years. Aim #2 will be addressed by performing a secondary analysis of a metabolic substudy (chaired by the principal investigator's primary mentor) of AIDS Clinical Trials Group study 384, which compared the use of protease inhibitor-based regimens with nonnucleoside reverse transcriptase-based regimens for the initial antiretroviral treatment of HIV-infected patients. Archived urine samples obtained at regular intervals through the duration of this substudy will be used to measure microalbuminuria levels. Taken together, the results of these studies will form the basis for future prevention and therapeutic trials targeted at both renal and cardiovascular diseases in HIV-infected patients. The proposed research will foster the principal investigator's clinical research career development, as supervised by established independent investigators (primary mentor: Michael P. Dub6) in the fields of HIV metabolic and renal complications, renal vascular and glomerular pathology, and clinical trials design and implementation.

描述（由申请人提供）：越来越多地报道了感染HIV的患者的肾脏和心血管疾病，可能会相互关联。总蛋白尿是一种广泛使用的肾脏疾病的初始筛查标记，在HIV感染的患者中非常普遍。在一般人群中，蛋白尿也与全身内皮功能障碍有关，这是未来心血管事件的预测指标。因此，我们假设内皮功能障碍可能与HIV感染人群中蛋白尿的高患病率有关。此外，由于蛋白酶抑制剂与内皮功能障碍有关，因此我们假设这类抗逆转录病毒可能会特别导致肾小球内皮疾病，最初表现为微藻尿症。这项研究的具体目的是（1）确定HIV感染患者的蛋白尿与全身内皮功能障碍之间的关系，（2）确定基于蛋白酶的HAART对HIV感染的患者的微量白蛋白尿的影响。为了解决AIM＃1，我们建议对印第安纳大学医学中心关心的HIV感染受试者进行预期的同类研究。具体而言，超声测量的流动介导的跑步动脉的扩张（对内皮功能的生理测量），脂质，胰岛素和葡萄糖水平，人类学成分，生活方式因素，生活方式因素以及两个受HIV感染的组的血压（具有持久性蛋白尿的蛋白尿vss），并将其再次相比，并将其再次相比。 AIM＃2将通过对AIDS临床试验小组研究384的代谢质量（由主要研究者的主要指导者主持）进行次要分析，该研究比较了基于蛋白酶抑制剂的基于蛋白酶的基于蛋白酶抑制剂的治疗方法与非核苷逆转录酶基于基于蛋白酶的抗逆转录病毒治疗HIV患者的抗逆转录病毒治疗方案。在该物质的持续时间内定期获得的尿液样品将用于测量微量白蛋白尿水平。综上所述，这些研究的结果将构成针对HIV感染患者的肾脏和心血管疾病的未来预防和治疗试验的基础。拟议的研究将在HIV代谢和肾脏并发症，肾脏血管和肾小球病理学以及临床试验设计和实施中，由既定的独立研究者（主要导师：Michael P. Dub6）的既定独立研究者（主要导师：Michael P. Dub6）的监督促进了首席研究者的临床研究职业发展。