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

Abstract

ObjectiveHigh rates of albuminuria are observed among HIV-infected individuals on stable antiretroviral therapy (ART). Though pro-inflammatory and pro-fibrotic responses are described as components of albuminuria in the general population, it is unclear how these responses are associated to albuminuria in ART-treated chronic HIV. We investigated the relationship of monocyte subsets and urine inflammatory and fibrotic biomarkers to albuminuria in ART-treated HIV-infected participants.Design and MethodsCross-sectional analyses were performed on Hawaii Aging with HIV-cardiovascular disease study cohort participants who were required at entry to be ≥40 years old and on ART ≥3 months. Monocyte subpopulations were determined in banked peripheral blood mononuclear cells (PBMC) using multi-parametric flow-cytometry. Entry random urine samples were assessed for albumin-to-creatinine ratios (UACR). Urine samples were measured for inflammatory and fibrotic biomarkers using Luminex technology.ResultsAmong 96 HIV-infected subjects with measured UACR (87% male, 59% Caucasian, and 89% undetectable HIV RNA with median CD4 of 495.5 cells/μL), 18 patients (19%) had albuminuria. Non-classical (CD14low/+CD16++) monocytes were significantly elevated in subjects with albuminuria (p = 0.034) and were correlated to UACR (r = 0.238, p = 0.019). Elevated non-classical monocyte counts were significant predictors of worsening albuminuria, independent of traditional- and ART-associated risk factors (β = 0.539, p = 0.007). Urine TGF-β1 and collagen-IV were significantly higher in albuminuric compared to non-albuminuric participants (TGF-β1; p = 0.039 and collagen-IV; p = 0.042). Urine TGF-β1 was significantly correlated with non-classical monocyte counts (r = 0.464, p = 0.017).ConclusionAlterations in monocyte subpopulations and urine pro-fibrotic factors may play a role in kidney dysfunction during chronic HIV infection and warrants further study.

Urinary Transforming Growth Factor-Beta 1 (uTGF-β1) and Prevalent CKD Risk in HIV-Positive Patients in West Africa

“…The increased expression of TGF-β1 in persistent renal injury 17 manifests as increased urinary excretion of TGF-β1 18 . This has been documented in renal diseases associated with increase in extracellular matrix production,6, 7 including HIV-related nephropathy 10 . The finding of increased urinary excretion of TGF-β1 in patients with HIV and CKD was corroborated by our study.…”

“…Some studies in patients with CKD who are HIV-positive have demonstrated elevated levels of TGF-β1 in renal tissue, 8 serum, 9 and in the urine 10 of patients with HIV-associated nephropathy. Our study aim was to investigate the association of uTGF-β1 with prevalent CKD in HIV-positive patients in Nigeria.…”

WITHDRAWN: Macrophage-targeting Fasudil treatment protects liver from the ischemia/reperfusion injury by promoting M2 macrophage polarization

“…Macrophages/monocytes also play important roles in regulatory immunity, such as antigen presenting [4]. Recent studies showed that there are at least two types of macrophages or monocytes, M1 and M2 macrophages [6] or classical/inflammatory and patrolling/regulatory monocytes [7], respectively. M1 macrophages are the "killer" type macrophages, which promote inflammation and rapidly eliminate the pathogens but also cause tissue damage.…”

Residual Renal Function in Hemodialysis and Inflammation

“…We do not know whether the correlation found between microinflammation and RRF is a mere association or whether there is a causal link between non‐classical monocytes and RRF loss. In this sense, recent publications point to the fact that these non‐classical monocytes are high in patients infected with the human immunodeficiency virus (HIV) who suffer from albuminuria ( P = 0.034), and their authors have raised the possibility that they could play a role in renal dysfunction.…”