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


METHODS
Cross-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.


RESULTS
Among 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).


CONCLUSIONS
Alterations in monocyte subpopulations and urine pro-fibrotic factors may play a role in kidney dysfunction during chronic HIV infection and warrants further study.
Department of Tropical Medicine, University of Hawaii, Honolulu, Hawaii, United States of America.|Hawaii Center for AIDS, University of Hawaii, Honolulu, Hawaii, United States of America.
Brooks I
BI
Mitchell
Department of Tropical Medicine, University of Hawaii, Honolulu, Hawaii, United States of America.
Mary Margaret
MM
Byron
Department of Medicine, University of Hawaii, Honolulu, Hawaii, United States of America.
Roland C
RC
Ng
Hawaii Center for AIDS, University of Hawaii, Honolulu, Hawaii, United States of America.|Department of Medicine, University of Hawaii, Honolulu, Hawaii, United States of America.
Dominic C
DC
Chow
Department of Tropical Medicine, University of Hawaii, Honolulu, Hawaii, United States of America.|Hawaii Center for AIDS, University of Hawaii, Honolulu, Hawaii, United States of America.
Lishomwa C
LC
Ndhlovu
Department of Tropical Medicine, University of Hawaii, Honolulu, Hawaii, United States of America.|Hawaii Center for AIDS, University of Hawaii, Honolulu, Hawaii, United States of America.|Department of Medicine, University of Hawaii, Honolulu, Hawaii, United States of America.
Cecilia M
CM
Shikuma
D000368:Aged; D000419:Albuminuria / Q000150:complications*; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000652:urine; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D005260:Female; D005355:Fibrosis; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000652:urine*; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism; D012189:Retrospective Studies; D053773:Transforming Growth Factor beta1 / Q000652:urine*
D019380:Anti-HIV Agents; D015415:Biomarkers; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; D053773:Transforming Growth Factor beta1