Mitchell Brooks I, Byron Mary Margaret, Ng Roland C, Chow Dominic C, Ndhlovu Lishomwa C, Shikuma Cecilia M
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.
PLoS One. 2016 Apr 20;11(4):e0153758. doi: 10.1371/journal.pone.0153758. eCollection 2016.
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.
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.
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).
Alterations in monocyte subpopulations and urine pro-fibrotic factors may play a role in kidney dysfunction during chronic HIV infection and warrants further study.
在接受稳定抗逆转录病毒治疗（ART）的HIV感染者中观察到高蛋白尿发生率。尽管在普通人群中促炎和促纤维化反应被描述为蛋白尿的组成部分，但尚不清楚这些反应在接受ART治疗的慢性HIV感染中如何与蛋白尿相关。我们调查了接受ART治疗的HIV感染参与者中单核细胞亚群、尿液炎症和纤维化生物标志物与蛋白尿之间的关系。
对夏威夷HIV与心血管疾病衰老研究队列的参与者进行横断面分析，这些参与者在入组时要求年龄≥40岁且接受ART治疗≥3个月。使用多参数流式细胞术在储存的外周血单核细胞（PBMC）中确定单核细胞亚群。评估入组时随机尿液样本的白蛋白与肌酐比值（UACR）。使用Luminex技术测量尿液样本中的炎症和纤维化生物标志物。
在96名测量了UACR的HIV感染受试者中（87%为男性，59%为白种人，89%的HIV RNA检测不到，CD4中位数为495.5个细胞/μL），18名患者（19%）有蛋白尿。非经典（CD14low/+CD16++）单核细胞在有蛋白尿的受试者中显著升高（p = 0.034），并且与UACR相关（r = 0.238，p = 0.019）。非经典单核细胞计数升高是蛋白尿恶化的显著预测因素，独立于传统和与ART相关的危险因素（β = 0.539，p = 0.007）。与无蛋白尿的参与者相比，有蛋白尿的参与者尿液中的TGF-β1和IV型胶原显著更高（TGF-β1；p = 0.039，IV型胶原；p = 0.042）。尿液TGF-β1与非经典单核细胞计数显著相关（r = 0.464，p = 0.017）。
单核细胞亚群和尿液促纤维化因子的改变可能在慢性HIV感染期间的肾功能障碍中起作用，值得进一步研究。
