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

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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.