Kidney Health Research Collaborative, Department of Medicine, San Francisco Veterans Affairs Medical Center and University of California, 533 Parnassus Avenue, U404, Box 0532, San Francisco, CA, 94143, USA.
Department Epidemiology, and Biostatistics, University of California, San Francisco, CA, USA.
BMC Nephrol. 2019 Jan 3;20(1):4. doi: 10.1186/s12882-018-1192-y.
HIV-positive persons bear an excess burden of chronic kidney disease (CKD); however, conventional methods to assess kidney health are insensitive and non-specific for detecting early kidney injury. Urinary biomarkers can detect early kidney injury, and may help mitigate the risk of overt CKD.
Cross-sectional study of HIV-positive persons in the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study. We measured levels of 14 biomarkers, capturing multiple dimensions of kidney injury. We then evaluated associations of known CKD risk factors with urine biomarkers using separate multivariable adjusted models for each biomarker.
Of the 198 participants, one third were on HAART and virally suppressed. The vast majority (95%) had preserved kidney function as assessed by serum creatinine, with a median eGFR of 103 ml/min/1.73 m (interquartile range (IQR): 88, 116). In our multivariable analyses, the associations of each CKD risk factor with urinary biomarker levels varied in magnitude. For example, HIV viral load was predominantly associated with elevations in interleukin(IL)-18, and albuminuria, while higher CD4 levels were associated with lower monocyte chemoattractant protein-1 (MCP-1) and β2-microglobulin. In contrast, older age was significantly associated with elevations in α1-microglobulin, kidney injury marker-1, clusterin, MCP-1, and chitinase-3-like protein-1 levels, as well as lower epidermal growth factor, and uromodulin levels.
Among HIV-positive persons, CKD risk factors are associated with unique and heterogeneous patterns of changes in urine biomarkers levels. Additional work is needed to develop parsimonious algorithms that integrate multiple biomarkers and clinical data to discern the risk of overt CKD and its progression.
HIV 阳性者患有慢性肾脏病（CKD）的负担过重；然而，评估肾脏健康的常规方法对检测早期肾脏损伤不敏感且特异性不强。尿液生物标志物可检测早期肾脏损伤，并可能有助于降低显性 CKD 的风险。
对多中心艾滋病队列研究和妇女艾滋病研究机构间研究中的 HIV 阳性者进行横断面研究。我们测量了 14 种生物标志物的水平，这些标志物可捕捉肾脏损伤的多个维度。然后，我们使用每个生物标志物的单独多变量调整模型评估已知 CKD 危险因素与尿液生物标志物之间的关联。
在 198 名参与者中，有三分之一正在接受高效抗逆转录病毒治疗（HAART）并病毒抑制。绝大多数（95%）的参与者通过血清肌酐评估肾功能正常，估计肾小球滤过率（eGFR）中位数为 103ml/min/1.73m（四分位间距（IQR）：88,116）。在我们的多变量分析中，每个 CKD 危险因素与尿液生物标志物水平的关联在幅度上有所不同。例如，HIV 病毒载量主要与白细胞介素（IL）-18 和白蛋白尿的升高有关，而较高的 CD4 水平与较低的单核细胞趋化蛋白-1（MCP-1）和β2-微球蛋白有关。相比之下，年龄较大与 α1-微球蛋白、肾损伤标志物-1、簇蛋白、MCP-1 和几丁质酶-3 样蛋白-1水平的升高以及表皮生长因子和尿调素水平的降低显著相关。
在 HIV 阳性者中，CKD 危险因素与尿液生物标志物水平的独特和异质变化模式相关。需要进一步研究来开发简洁的算法，该算法可整合多种生物标志物和临床数据来辨别显性 CKD 及其进展的风险。
