Burden of Chronic Kidney Disease in HIV Infection

描述(由申请人提供)： 这项应用的总体目标是支持研究人员的教育和临床研究，从而在专注于艾滋病毒相关肾脏疾病的以患者为导向的研究中独立发展。有了职业发展奖和一项教学和科学培训计划，这些目标将通过以下方式实现：1)在研究方法、统计分析、科学交流和手稿准备方面获得直接指导；2)获得临床研究研究生培训计划的正式指导，以及队列设计/统计分析和遗传流行病学方面的高级课程；3)在约翰·霍普金斯医学院和公共卫生学院以及韦尔奇预防、流行病学和临床研究中心提供的支持环境下，在导师和合作者的指导和投入下实施研究计划。通过高效抗逆转录病毒疗法(HAART)，艾滋病毒感染者的存活率显著提高；因此，肾脏疾病等慢性疾病日益受到关注。该提案的总体目标是使用血清肌酐和胱抑素C来量化艾滋病毒感染者慢性肾脏疾病(CKD)的负担，并调查艾滋病毒和宿主相关因素是否参与艾滋病毒阳性个人CKD的发生和发展。这项建议将使用两个独特的研究人群：1)从多中心艾滋病队列研究(MACS)和妇女机构间艾滋病毒研究(WIHS)队列中获得长期随访的种族多样化的艾滋病毒阳性个人人数；以及2)通过约翰·霍普金斯艾滋病毒/艾滋病服务招募的艾滋病毒阳性个人的诊所研究人群。这项建议将提供：1)艾滋病毒相关慢性肾脏病在美国的当前流行病学及其对死亡率的影响；2)基于胱抑素C的慢性肾脏病患病率与肾功能的血肌酐估计值的比较；3)与HAART和艾滋病毒疾病阶段相关的慢性肾脏病发生和发展风险的调查；以及4)Myh9与慢性肾脏病进展和特定的肾脏组织病理学结果之间的关系的确认。 公共卫生相关性：这项建议将对在这一高危人群中筛查和识别慢性肾脏病具有重要意义。它将确定慢性肾脏病在艾滋病毒感染自然历史中的影响，并确定在HAART时代慢性肾脏病的危险因素。这将产生HIV相关CKD的潜在机制，最终可能导致HIV相关CKD的诊断和预后标记物的发展。

DESCRIPTION (provided by applicant): The overall goal of this application is to support the education and clinical research of the investigator leading to an independent career in patient-oriented research focused on HIV-related kidney disease. With the career development award and a program of didactic and scientific training, the goals will be achieved by: 1) receiving direct mentorship in study methods, statistical analysis, scientific communication and manuscript preparation 2) obtaining formal instruction in the Graduate Training Program in Clinical Investigation and advanced courses in cohort design/ statistical analysis and genetic epidemiology and 3) implementing the research proposal with guidance and input from mentors and collaborators in the supportive environment offered by the Johns Hopkins Schools of Medicine and Public Health, and the Welch Center for Prevention, Epidemiology and Clinical Research. Survival of HIV-infected individuals has improved significantly with highly active antiretroviral therapy (HAART); consequently, chronic illnesses such as kidney disease are of increasing concern. The overall aim of the proposal is to quantify the burden of chronic kidney disease (CKD) in HIV-infected individuals using serum creatinine and cystatin C and to investigate whether HIV- and host-related factors are involved in the development and progression of CKD in HIV-positive individuals. This proposal will use two unique study populations: 1) a large, racially diverse population of HIV-positive individuals with extended follow-up from the Multicenter AIDS Cohort Study (MACS) and the Womens' Interagency HIV Study (WIHS) cohorts; and 2) a clinic-based study population of HIV-positive individuals recruited through the Johns Hopkins HIV/AIDS Service. This proposal will provide: 1) the current epidemiology of HIV-related CKD in the U.S. and its impact on mortality; 2) a comparison of the prevalence of CKD based on cystatin C versus serum creatinine estimates of kidney function; 3) an investigation of the risk of CKD development and progression related to HAART and HIV disease stage; and 4) a validation of the association of MYH9 with CKD progression and specific renal histopathologic findings. PUBLIC HEALTH RELEVANCE: This proposal will have important implications in screening and identifying CKD in this high risk population. It will determine the impact of CKD in the natural history of HIV infection and determine risk factors for CKD during the HAART era. It will yield a potential mechanism for HIV-related CKD which may ultimately lead to the development of diagnostic and prognostic markers for HIV-related CKD.