Albuminuria Is Associated with Elevated Acute Phase Reactants and Proinflammatory Markers in HIV-Infected Patients Receiving Suppressive Combination Antiretroviral Therapy

Abstract

Albuminuria among HIV-infected individuals has been found to be associated with cardiovascular disease (CVD) and mortality. Inflammation has been associated with albuminuria. The pathophysiology of albuminuria in HIV-infected individuals is poorly understood. We investigated the association of albuminuria with inflammatory biomarkers among HIV-infected individuals on combination antiretroviral therapy (cART). This is a cross-sectional analysis of participants enrolled in the Hawaii Aging with HIV-Cardiovascular Cohort. Plasma inflammatory biomarkers were assessed using the Milliplex Human Cardiovascular disease multiplex assays. A random urine sample was collected for albumin measurement. Albuminuria was defined as urine albumin-tocreatinine ratio of ‡ 30 mg/g. Framingham risk score was calculated and divided into three classes. Simple and multivariable logistic regression analyses were utilized to assess the correlation between plasma inflammatory biomarkers and albuminuria and were adjusted for Framingham risk category. Among 111 HIV-infected patients [median (IQR) age of 52 (46-57) years, 86% male, median (IQR) CD4 count of 489 (341-638) cells/ mm 3 , 85% with HIV RNA < 50 copies/ml], 18 subjects (16.2%) had moderately increased albuminuria (albuminuria range between 30 and 300 mg/g) and 2 subjects (1.8%) had severely increased albuminuria (albuminuria more than 300 mg/g). In multivariable logistic models, sE-selectin, sVCAM-1, CRP, SAA, and SAP remained significantly associated with albuminuria after adjustment of CVD risk factors. This study showed an association between inflammation and albuminuria independent of previously reported risk factors for albuminuria in HIV-infected subjects who were on combination antiretroviral therapy (cART). Chronic inflammation despite potent antiretroviral treatment may contribute to higher rates of albuminuria among HIVinfected patients.

Urinary albumin-to-creatinine ratio is associated with endothelial dysfunction in HIV-infected patients receiving antiretroviral therapy

“…Although there is overwhelming evidence of an association between UACR and endothelial dysfunction in different clinical settings 40 41 , this association was little explored in HIV positive patients 21 22 . O-Charoen et al .…”

“…O-Charoen et al . 21 found that elevation of endothelial dysfunction markers, like soluble E-selectin and vascular cell adhesion protein-1, were significantly associated with albuminuria after adjustment for CV risk factors in HIV-infected patients receiving suppressive combination antiretroviral therapy 21 . However, Gupta et al .…”

“…The high prevalence of MA and endothelial dysfunction in HIV-infected patients on HAART might support the existence of an association between these conditions. Interestingly, elevation of endothelial dysfunction markers like soluble E-selectin and vascular cell adhesion protein-1 were significantly associated with albuminuria after adjustment for CV risk factors 21 . To the best of our knowledge, only one study has addressed this issue in HIV positive patients exploring endothelial function by measurement of brachial flow-mediated vasodilation 22 ; specifically, Gupta et al .…”

Associations between plasma tenofovir concentration and renal function markers in HIV-infected women

“… 25 In 85% of HIV-infected adults taking TDF-based ART, the presence of albuminuria was associated with inflammatory biomarkers. 26 Nevertheless, the authors did not adjust for all baseline characteristics such as the use of angiotensin receptor blockers or angiotensin converting enzyme inhibitors, age and hypertension. Inflammatory biomarkers in another study 27 were higher in untreated HIV-infected participants compared to both HIV-infected participants (TDF-based ART and virally suppressed) and uninfected controls.…”

Elevation of Non-Classical (CD14+/lowCD16++) Monocytes Is Associated with Increased Albuminuria and Urine TGF-β1 in HIV-Infected Individuals on Stable Antiretroviral Therapy

“…HIV-infected individuals on stable ART show higher rates of albuminuria, as compared to the general population. Chronic low-grade inflammation may contribute to the development of albuminuria and renal dysfunction, which both pro-inflammatory and pro-fibrotic responses are important components [ 18 , 20 , 40 – 46 ]. However, mechanisms of albuminuria that occurs during ART-treated chronic HIV infection have been primarily focused on the pro-inflammatory arm.…”