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

可卡因依赖的非裔美国人的炎症和亚临床肾损伤

• 批准号: 7835557
• 负责人: ELIZABETH Grooms NESMITH
• 金额: $ 7.35万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-15 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7835557
• 关键词: 18 year old; Adverse effects; African American; Age; Ambulatory Care Facilities; American; Autoimmune Process; Blood Transfusion; Blood Vessels; C-reactive protein; Caucasians; Caucasoid Race; Clinical; Clinical Trials; Cocaine; Cocaine Users; Communities; Control Groups; DSM-IV; Data; Dependency; Diabetes Mellitus; Diagnosis; Diagnostic and Statistical Manual of Mental Disorders; Disease; Early Diagnosis; Education; Exhibits; Failure; Feasibility Studies; Future; Glycosylated hemoglobin A; Goals; HIV; Heart; Hypertension; Income; Infection; Inflammation; Inflammatory; Interleukin-6; Interview; Investigation; Kidney; Kidney Diseases; Kidney Failure; Knowledge; Life Style; Link; Literature; Liver; Lung; Malignant Neoplasms; Medical; Mental Health; Microalbuminuria; Mission; Morbidity - disease rate; National Institute of Drug Abuse; Non-Steroidal Anti-Inflammatory Agents; Organ failure; Participant; Patient Self-Report; Physiological; Physiology; Pilot Projects; Pregnancy; Protein C; Psychiatry; Race; Recruitment Activity; Renal function; Reporting; Research; Research Personnel; Respondent; Risk; Sampling; Science; Serum; Severities; Steroids; Structure; Substance Abuse Treatment Centers; Testing; Time; Tumor Necrosis Factor-alpha; White Blood Cell Count procedure; addiction; biobehavior; case control; cocaine use; design; dosage; health disparity; improved; medically underserved population; meetings; mortality; primary outcome; public health relevance; salicylate; sex; statistics; substance abuse treatment

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.

描述（由申请人提供）：本项目的总体目标是检查可卡因依赖对非裔美国人（AAs）肾脏生理学的影响。可卡因依赖性AA存在因可卡因使用而导致亚临床肾损伤的风险，但几乎没有数据可以指导临床医生做出药物滥用和药物治疗决策。已证明辅酶A影响肾功能，但这些影响的程度和机制尚不清楚。炎症成分白细胞介素-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变化可能导致肾损伤。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性AA是否表现出与高水平IL-6、TNF-1和CRP相关的血管内皮损伤引起的亚临床肾病体征。具体目标是：1）确定可卡因依赖性AA中亚临床肾损伤的存在（通过微量白蛋白尿水平），和2）检查可卡因依赖性AA中微量白蛋白尿水平与炎性组分IL-6、TNF-1和CRP的血清水平之间的关系。有足够的把握度来检验以下假设：1）可卡因依赖性AA中的微量白蛋白尿水平将高于年龄/性别匹配的未使用可卡因的AA对照组中的微量白蛋白尿水平; 2）可卡因依赖性AA中的微量白蛋白尿水平将与IL-6、TNF-1和CRP的血清水平相关。将使用应答者驱动抽样从药物滥用治疗中心和社区招募至少18岁（n =51）的可卡因依赖性AA。将从精神科门诊和社区招募不依赖可卡因的AA（对照组; n = 51）。可卡因依赖性将使用精神疾病诊断和统计手册（DSM-IV）轴I疾病（SCID）的结构化临床访谈和过去30天中至少4天可卡因使用的自我报告来定义。受试者将被排除在过去2周内输血，高血压（BP > 140/90 mm/Hg），感染（CRP > 10 mg/L），不受控制的糖尿病（HbA 1c>15%），类固醇，NSAID或水杨酸盐使用> 1个月，预先存在的肾脏疾病，HIV，癌症，自身免疫性疾病和怀孕。主要结果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，人口统计学，收入和教育变量，以及身心健康功能。这项研究与国家药物滥用研究所的使命是一致的，以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作出可卡因依赖的治疗决定，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，减少可卡因相关的发病率和死亡率。公共卫生相关性：可卡因依赖性AA存在亚临床肾损伤的风险，可能是由于炎症原因。在医疗服务不足的人群中，这一点很重要，在这些人群中，与可卡因有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为可卡因依赖做出治疗决定，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，减少非裔美国人与可卡因相关的发病率和死亡率。