Inflammation and Sub-Clinical Renal Damage in Cocaine-Dependent African Americans

描述（由申请人提供）：该项目的总体目标是研究可卡因依赖对非裔美国人（AAs）肾脏生理的影响。可卡因依赖的AAs有因可卡因使用而导致亚临床肾损害的风险，但很少有数据可以指导临床医生做出药物滥用和医疗决策。可卡因已被证明对肾功能有影响，但这些影响的程度和机制尚不清楚。炎症成分白介素-6 （IL-6）、肿瘤坏死因子- α (TNF-1)和c反应蛋白（CRP）升高引起的血管内皮改变可能导致肾损害。可卡因使用与IL-6、TNF-1和CRP水平升高之间的联系已被报道，但需要更多的研究，特别是在AA亚群中。本病例对照初步研究的短期目标是确定可卡因依赖的AAs是否表现出由高水平IL-6、TNF-1和CRP相关的血管内皮损伤引起的亚临床肾脏疾病的迹象。具体目的是：1)确定可卡因依赖的AAs中存在亚临床肾损害（通过微量白蛋白尿水平），2)检查微量白蛋白尿水平与可卡因依赖的AAs中血清炎症成分IL-6、TNF-1和CRP水平之间的关系。功率足以验证以下假设：1)可卡因依赖的AAs的微量白蛋白尿水平将高于年龄/性别匹配的不使用可卡因的AAs对照组的微量白蛋白尿水平；2)可卡因依赖AAs的微量白蛋白尿水平与血清IL-6、TNF-1和CRP水平相关。将从药物滥用治疗中心和社区招募至少18岁的可卡因依赖者（n =51），采用受访者驱动的抽样方法。不依赖可卡因的AAs（对照；n = 51）将从精神科门诊诊所和社区招募。可卡因依赖将使用精神障碍诊断与统计手册（DSM-IV） I轴障碍（SCID）的结构化临床访谈和自我报告过去30天中至少4天的可卡因使用情况来定义。受试者将被排除在过去2周内输血、高血压（血压140/90 mm/Hg）、感染（CRP >10mg/L）、未控制的糖尿病（HbA1c >15%）、类固醇、非甾体抗炎药或水杨酸盐使用>1个月、既往肾病、HIV、癌症、自身免疫性疾病和妊娠。主要结局变量是微量白蛋白尿水平和血清IL-6、TNF-1和CRP水平。协变量分析的次要变量包括成瘾严重程度、人口统计、收入和教育变量以及身心健康功能。这项研究符合国家药物滥用研究所的使命，即改善药物滥用治疗和医疗服务不足人群的健康差距。所获得的知识可用于制定可卡因依赖的治疗决策，并设计社区一级的临床试验，通过早期诊断和治疗依赖的肾脏后果来减少可卡因相关的发病率和死亡率。公共卫生相关性：可卡因依赖的AAs有可能由炎症引起亚临床肾损害的风险。考虑到医疗服务不足的人群，这一点很重要，因为在这些人群中，与可卡因相关的肾衰竭风险可能未被识别和治疗。从这项研究中获得的知识可用于制定可卡因依赖的治疗决策，并设计社区一级的临床试验，通过早期诊断和治疗依赖的肾脏后果来减少非洲裔美国人的可卡因相关发病率和死亡率。

DESCRIPTION (provided by applicant): The overall goal of this project is to examine the effects of cocaine dependency on renal physiology in African Americans (AAs). Cocaine-dependent AAs are at risk for sub-clinical renal damage resulting from cocaine use, yet little data exists to guide clinicians in making substance-abuse and medical treatment decisions. Cocaine has been shown to effect renal function, but the extent of these effects and the mechanisms responsible are not clear. Vascular endothelial changes from increases in inflammatory components interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-1), and C-reactive protein (CRP) may contribute to renal damage. Links between cocaine use and increased levels of IL-6, TNF-1, and CRP have been reported, but more research is needed, especially in the AA subpopulation. The short-term objective of this case-control pilot study is to determine if cocaine-dependent AAs exhibit signs of sub-clinical renal disease resulting from vascular endothelial damage associated with high levels of IL-6, TNF-1, and CRP. The specific aims are to: 1) determine the presence of sub-clinical renal damage (by microalbuminuria levels) in cocaine-dependent AAs, and 2) examine relationships between microalbuminuria levels and serum levels of inflammatory components IL-6, TNF-1, and CRP in cocaine-dependent AAs. Power is sufficient to test the hypotheses that 1) microalbuminuria levels in cocaine-dependent AAs will be greater than microalbuminuria levels in an age/sex-matched control group of AAs who do not use cocaine; and 2) microalbuminuria levels in cocaine-dependent AAs will correlate with serum levels of IL-6, TNF-1, and CRP. Cocaine-dependent AAs who are at least 18 years old (n =51) will be recruited from substance abuse treatment centers and the community using respondent-driven sampling. AAs who are not cocaine-dependent (controls; n = 51) will be recruited from the Department of Psychiatry outpatient clinics and the community. Cocaine-dependency will be defined using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Axis I Disorders (SCID), and by self-report of cocaine use for at least 4 days out of the last 30 days. Participants will be excluded for blood transfusion within last 2 weeks, hypertension (BP > 140/90 mm/Hg), infection (CRP >10mg/L), uncontrolled diabetes (HbA1c >15%), steroid, NSAID, or salicylate use > 1 month, pre-existing renal disease, HIV, cancer, autoimmune conditions, and pregnancy. Primary outcome variables are microalbuminuria levels and serum levels of IL-6, TNF-1, and CRP. Secondary variables for covariate analysis include addiction severity, demographic, income, and education variables, and physical and mental health functioning. This research is congruent with the mission of National Institute of Drug Abuse to improve substance-abuse treatment and health disparities in medically underserved populations. The knowledge gained could be used to make treatment decisions for cocaine dependency, and to design community-level clinical trials to reduce cocaine- related morbidity and mortality through early diagnosis and treatment o renal consequences of dependency. PUBLIC HEALTH RELEVANCE: Cocaine-dependent AAs are at risk for sub-clinical renal damage possibly due to inflammatory causes. This is important when considered in the context of medically underserved populations, in whom cocaine-related risk for renal failure could go unrecognized and untreated. The knowledge gained from this research could be used to make treatment decisions for cocaine dependency, and to design community-level clinical trials to reduce cocaine-related morbidity and mortality in African Americans through early diagnosis and treatment of renal consequences of dependency.