HIV-Related Proteinuria and Endothelial Dysfunction

HIV 相关蛋白尿和内皮功能障碍

• 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
• 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

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）： HIV 感染者的肾脏和心血管疾病的报道越来越多，并且可能是相互关联的。总蛋白尿是广泛使用的肾脏疾病初步筛查标志物，在 HIV 感染患者中极为常见。在一般人群中，蛋白尿还与全身内皮功能障碍有关，这是未来心血管事件的预测因子。因此，我们推测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，我们推测此类抗逆转录病毒药物可能会特异性导致肾小球内皮疾病，最初表现为微量白蛋白尿。本研究的具体目的是 (1) 确定 HIV 感染患者蛋白尿与全身内皮功能障碍之间的关系，以及 (2) 确定基于蛋白酶抑制剂的 HAART 对 HIV 感染患者微量白蛋白尿的影响。为了实现目标#1，我们建议对印第安纳大学医学中心护理的艾滋病毒感染者进行一项前瞻性队列研究。具体来说，超声测量的血流介导的肱动脉扩张（内皮功能的生理测量）、血脂、胰岛素和葡萄糖水平、人体测量学、生活方式因素以及两个 HIV 感染者群体（持续性蛋白尿者与非感染者）的血压没有蛋白尿）将在基线时进行比较，并在两年内再次进行比较。目标#2将通过对艾滋病临床试验组研究384的代谢子研究（由主要研究者的主要导师主持）进行二次分析来解决，该研究比较了基于蛋白酶抑制剂的治疗方案与基于非核苷逆转录酶的治疗方案的使用HIV感染者的初始抗逆转录病毒治疗。在本次研究期间定期获得的存档尿液样本将用于测量微量白蛋白尿水平。总而言之，这些研究的结果将为未来针对艾滋病毒感染者的肾脏和心血管疾病的预防和治疗试验奠定基础。拟议的研究将促进主要研究者的临床研究职业发展，并由艾滋病毒代谢和肾脏并发症、肾血管和肾小球病理学以及临床试验设计和实施领域的独立研究者（主要导师：Michael P. Dub6）监督。 。

项目成果

Will there be an epidemic of HIV-related chronic kidney disease in sub-Saharan Africa? Too soon to tell.

撒哈拉以南非洲地区是否会流行艾滋病毒相关的慢性肾病？

• 发表时间: 2008-10
• 影响因子: 19.6
• 作者: Wools;Gupta, Samir K
• 通讯作者: Gupta, Samir K

Tenofovir-associated Fanconi syndrome: review of the FDA adverse event reporting system.

替诺福韦相关范可尼综合征：FDA 不良事件报告系统审查。

• 发表时间: 2008-02
• 影响因子: 4.9
• 作者: Gupta; Samir K
• 通讯作者: Samir K

Renal disease in an antiretroviral-naive HIV-infected outpatient population in Western Kenya.

肯尼亚西部未接受过抗逆转录病毒治疗的艾滋病毒感染门诊患者的肾脏疾病。

• 发表时间: 2007-08
• 作者: Wools;Gupta, Samir K;Muloma, Eva;Owino;Sidle, John;Aubrey, Ryan W;Shen, Jianzhao;Kipruto, Kirwa;Zwickl, Beth E;Goldman, Mitchell
• 通讯作者: Goldman, Mitchell