The observed higher prevalence of albuminuria among HIV-infected patients has been strongly associated with cardiovascular disease and higher mortality. In HIV-seronegative patients with metabolic syndrome, malignancies and infections, pro-inflammatory cytokines, and acute phase reactants have been associated with albuminuria. However, the pathophysiology of albuminuria in HIV-seropositive individuals is poorly understood. We investigated the association of albuminuria with inflammatory biomarkers among HIV-infected patients on combination antiretroviral therapy.
This is a cross-sectional analysis of the entry data of the participants enrolled in the Hawai‘i Aging with HIV-Cardiovascular Cohort. Participants were ≥ 40 years old, lived in Hawai‘i, documented HIV-positive, and had been on antiretroviral therapy for at least 6 months prior to recruitment. Albuminuria was defined as urine albumin-to-creatinine ratio (ACR) of 30 mg/g or higher, as assessed from single random urine collection. Microalbuminuria was defined as urine ACR between 30 and 300 mg/g and macroalbuminuria as urine ACR more than 300 mg/g. Plasma inflammatory biomarkers were assessed by multiplexing using Milliplex Human Cardiovascular Disease panels. Differences in clinical and laboratory characteristics between subjects with and without albuminuria were compared using a non-parametric Wilcoxon rank test for continuous variables and a chi-squared test for categorical variables. Univariate and multivariate logistic regression analyses were utilized to assess the association between presence of albuminuria as the dependent variable and plasma biomarkers as independent variables. Log-transformed plasma inflammatory biomarkers with P-value less than .1 in univariate logistic regression analysis were selected for examination in separate multivariate logistic regression models, adjusting for previously reported risk factors for albuminuria (age, gender, race, diabetes, hypertension, CD4 percent, current ritonavir, and tenofovir use).
Among a cohort of 111 HIV-infected patients (median age of 52 (Q1: 46, Q3: 57); male 86%; diabetes 6%; hypertension 33%; median CD4 count of 489 cells/mm3(Q1:341, Q3: 638); HIV RNA PCR < 48 copies/ml 85%), eighteen subjects (16.2%) had microalbuminuria, and two subjects (1.8%) had macroalbuminuria. There was no significant difference in CD4 count and HIV viral loads between patients with and without albuminuria. In univariate logistic regression analysis, higher levels of log-transformed soluble E-selectin (sE-selectin), soluble vascular cell adhesion molecule 1 (sVCAM-1), tissue plasminogen activator inhibitor-1 (tPAI-1), C-reactive protein (CRP), serum amyloid A (SAA), serum amyloid P (SAP), interleukin-1β, interleukin-8, and tumor necrosis factor-α (TNF-α) were associated with albuminuria (P < .10). In multivariate logistic regression models, sE-selectin, sVCAM-1, tPAI-1, CRP, and SAP remained significant (P < .05) even after adjustment for previously reported risk factors for albuminuria.
This study has shown an association between inflammation and albuminuria independent of previously reported risk factors for albuminuria in HIV-infected subjects on stable combination antiretroviral therapy. Chronic low-grade inflammation despite potent antiretroviral treatment may be one of the factors causing higher rates of albuminuria among HIV-infected patients. Future studies are needed to further elucidate the pathophysiologic mechanisms of chronic inflammation in HIV and its impact on kidney disease.