Early-Stage Chronic Kidney Disease in HIV-infected Individuals

描述（由申请人提供）：HIV感染者发生终末期肾病（ESRD）的风险是HIV血清阴性个体的10倍。在一般人群中，蛋白尿通常是慢性肾脏疾病（CKD）最早可检测的标志物，即使非常低水平的蛋白尿也可预测未来的心血管事件和死亡率。在高活性抗逆转录病毒治疗（HAART）时代的横断面研究表明，蛋白尿在艾滋病毒感染者中的患病率是艾滋病毒血清阴性者的3- 5倍。然而，关于蛋白尿随时间的自然史或蛋白尿对该人群肾功能丧失或心血管疾病的影响的数据很少。我们建议进行一项密集的队列研究，包括从约翰霍普金斯大学HIV临床队列和艾滋病与静脉注射经验（ALIVE）研究中招募的同等数量的HIV感染者和HIV阴性的肾功能正常的个体（估计肾小球滤过率（GFR） bbb60 mL/min/1.73 m2）。这些人群的非法药物使用和丙型肝炎感染率较高，这与CKD风险增加有关。将对蛋白尿受试者进行过度抽样，以便在hiv感染组和hiv阴性组中对蛋白尿和正常蛋白尿受试者进行大致相同数量的跟踪调查。本研究的目的是：1)确定HIV感染和蛋白尿对GFR变化（通过碘醇清除量测定）和颈动脉内膜-中膜厚度变化（心血管疾病的替代标志物）的影响；2)评估该人群中肾损伤和GFR的新生物标志物；3)评估HIV相关CKD的潜在致病机制（包括尿中测量的病毒负担和免疫激活）。我们计划用“金标准”测量技术来表征GFR的纵向变化，这是新颖的，将成为许多基于估计GFR的hiv相关CKD研究的关键补充。我们的建议针对hiv感染个体的早期CKD的自然历史和发病机制，这一阶段的疾病既没有得到充分的研究，也可能是最容易干预的。

DESCRIPTION (provided by applicant): HIV-infected individuals have a 10-fold higher risk of developing end-stage renal disease (ESRD) than HIV- seronegative individuals. In the general population, albuminuria is typically the earliest detectable marker of chronic kidney disease (CKD), and even very low levels of albuminuria are predictive of future cardiovascular events and mortality. Cross-sectional studies in the era of highly active antiretroviral therapy (HAART) indicate that the prevalence of albuminuria is 3- to 5-times higher in HIV-infected individuals than in HIV-seronegative persons. However, few data are available regarding the natural history of albuminuria over time or of the implications of albuminuria for loss of kidney function or cardiovascular disease in this population. We propose to conduct an intensive cohort study that includes equal numbers of HIV-infected and HIV-negative individuals with normal kidney function (estimated glomerular filtration rate (GFR) > 60 mL/min/1.73 m2), recruited from the Johns Hopkins HIV Clinical Cohort and the AIDS Link to the Intravenous Experience (ALIVE) study. These cohorts have high rates of illicit drug use and hepatitis C infection, which have been linked to increased CKD risk. Albuminuric subjects will be over-sampled, so that approximately equal numbers of albuminuric and normoalbuminuric subjects will be followed in the HIV-infected and HIV-negative groups. The aims of our study are to 1) determine the implications of HIV infection and albuminuria for changes in GFR (determined by serial measures of iohexol clearance) and for changes in carotid intima-media thickness (a surrogate marker of cardiovascular disease), 2) evaluate novel biomarkers of kidney injury and GFR in this population, and 3) assess potential pathogenic mechanisms of HIV-related CKD (including viral burden measured in urine and immune activation). Our plan to characterize longitudinal changes in GFR with a 'gold standard' measurement technique is novel and will be a key complement to the many studies of HIV-related CKD that are based on estimated GFR. Our proposal targets the natural history and pathogenesis of early-stage CKD in HIV-infected individuals, a phase of disease that is both understudied and potentially most amenable to intervention. PUBLIC HEALTH RELEVANCE: People who are infected with HIV have a high risk of developing kidney disease leading to kidney failure. Chronic kidney disease is also a strong risk factor for heart disease. In a sample of HIV-infected and HIV- negative research participants, we propose to study clinical markers and contributing factors in the progression of kidney disease, and the association between kidney disease and heart disease.