Increased Prevalence of Albuminuria in HIV-Infected Adults with Diabetes

et al. (2011) Increased Prevalence of Albuminuria in HIV-Infected Adults with Diabetes. PLoS ONE 6(9): e24610. doi:10.1371/journal.pone.0024610 Increased Prevalence of Albuminuria in HIV-Infected Adults with Diabetes Peter S. Kim 0 Christian Woods 0 Lauren Dutcher 0 Patrick Georgoff 0 Alice Rosenberg 0 Jo Ann M. Mican 0 Jeffrey B. Kopp 0 Margo A. Smith 0 Colleen Hadigan 0 Sarah Pett, University of New South Wales, Australia 0 1 National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda , Maryland, United States of America, 2 Department of Infectious Disease, Washington Hospital Center , Washington, D. C. , United States of America, 3 University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America, 4 National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Bethesda, Maryland , United States of America Objective: HIV and type 2 diabetes are known risk factors for albuminuria, but no previous reports have characterized albuminuria in HIV-infected patients with diabetes. Research Design and Methods: We performed a cross-sectional study including 73 HIV-infected adults with type 2 diabetes, 82 HIV-infected non-diabetics, and 61 diabetic control subjects without HIV. Serum creatinine .1.5 mg/dL was exclusionary. Albuminuria was defined as urinary albumin/creatinine ratio .30 mg/g. Results: The prevalence of albuminuria was significantly increased among HIV-infected diabetics (34% vs. 13% of HIV nondiabetic vs. 16% diabetic control, p = 0.005). HIV status and diabetes remained significant predictors of albuminuria after adjusting for age, race, BMI, and blood pressure. Albumin/creatinine ratio correlated significantly with HIV viral load (r = 0.28, p = 0.0005) and HIV-infected subjects with albuminuria had significantly greater cumulative exposure to abacavir (p = 0.01). In an adjusted multivariate regression analysis of HIV-infected subjects, the diagnosis of diabetes (p = 0.003), higher HIV viral load (p = 0.03) and cumulative exposure to abacavir (p = 0.0009) were significant independent predictors of albuminuria. Conclusions: HIV and diabetes appear to have additive effects on albuminuria which is also independently associated with increased exposure to abacavir and HIV viral load. Future research on the persistence, progression and management of albuminuria in this unique at-risk population is needed. - Funding: The study was funded and conducted by the National Institute of Allergy and Infectious Diseases and the National Institute of Diabetes and Digestive and Kidney Diseases Intramural Research Programs and the Washington Hospital Center, Department of Infectious Diseases. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. Kidney disease is an important contributor to HIV/AIDSrelated morbidity and mortality. As the life expectancy of HIVinfected patients increases with the use of antiretroviral therapy, chronic medical conditions such as renal failure are increasingly prevalent [1,2,3]. In addition, type 2 diabetes is increased among persons living with HIV and is associated with cumulative exposure to antiretroviral therapy [4,5,6]. Though the influences of both diabetes and HIV infection on kidney disease are wellrecognized, there is very little known about kidney disease among HIV-infected individuals with type 2 diabetes. Albuminuria is a marker of kidney damage, and is associated with increased cardiovascular disease and renal mortality and morbidity [7,8,9]. Prior to the widespread use of highly active antiretroviral therapy (HAART), studies identified a strikingly high prevalence of microalbuminuria (defined as urine albumin to creatinine ratio greater than 30 mg/g, but less than 300 mg/g), ranging from 19% to 30% among HIV-infected populations [10,11]. More recent investigations of microalbuminuria in the post-HAART era found a prevalence between 8.7% and 11% among persons living with HIV [12,13]. Albuminuria is common in type 2 diabetes in the absence of HIV. In one large longitudinal cohort of adults with type 2 diabetes, 25% of participants had microalbuminuria ten years after the diagnosis of diabetes [14]. Given the increased risk of microalbuminuria associated with both HIV and diabetes, we evaluated a cohort of HIV-infected adults with type 2 diabetes to assess the prevalence of albuminuria, as compared to control groups with type 2 diabetes without HIVinfection and HIV-infection without diabetes. Materials and Methods Subjects Subjects were patients who attended HIV clinic at the National Institute of Allergy and Infectious Diseases (NIAID) outpatient clinic in Bethesda, MD or the Washington Hospital Center Infectious Diseases clinic in Washington, DC between March 2007 and February 2009. Potentially eligible participants were notified of the available research studies at routine clinic appointments and returned for subsequent research visits if interested. Participants were 73 HIV-infected adults with type 2 diabetes (defined by one or more of the following: documented diagnosis of type 2 diabetes, ICD9 codes 250.0250.9, fasting plasma glucose $ 126 mg/dL on 2 or more occasions, and/or casual plasma glucose $ 200 mg/dL and the presence of symptoms; subjects with type 1 diabetes were excluded) and 82 HIV-infected adults without diabetes or hyperglycemia (fasting glucose ,110 mg/dl, no random glucose .200 mg/dl in the past 2 years, no known diagnosis of diabetes and not on antihyperglycemic agents). Subjects with known current pregnancy, active opportunistic infection or malignancy, and known end stage renal disease or creatinine .1.5 mg/dL were excluded from participation. Subjects with HIV and diabetes were enrolled in a study of the accuracy of hemoglobin A1c which has been published previously [15]. Non-diabetic HIV-infected participants were enrolled in a study of albuminuria, but only baseline assessments were available for use in this analysis. Specific matching strategies were not used for HIV-infected subjects with or without diabetes. The study protocols were approved by the NIAID, the National Institute of Diabetes and Digestive and Kidney Diseases, and Medstar Research Institute institutional review boards. Participants gave written informed consent. A physical exam and detailed medical history were completed and blood and urine samples were collected. A complete history of current and past antiretroviral therapy and current medications was recorded for all HIV-infected subjects. Measurements included serum creatinine, as well as urine albumin and creatinine. Albuminuria was defined as a urine albumin/creatinine ratio of .30 mg/g. To obtain a non-HIV-infected control group with type 2 diabetes, data from 61 adults with type 2 diabetes were obtained from MedSta (...truncated)