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尿液生物标志物与 HIV 感染和未感染男性肾功能下降的关联。

Associations of Urine Biomarkers with Kidney Function Decline in HIV-Infected and Uninfected Men.

机构信息

Kidney Health Research Collaborative, Department of Medicine, San Francisco Veterans Affairs Medical Center and University of California, San Francisco, California, USA.

Department of Medicine, University of California, Los Angeles, California, USA.

出版信息

Am J Nephrol. 2019;50(5):401-410. doi: 10.1159/000502898. Epub 2019 Sep 25.

Abstract

BACKGROUND

HIV-infected (HIV+) persons are at increased risk of chronic kidney disease, but serum creatinine does not detect early losses in kidney function. We hypothesized that urine biomarkers of kidney damage would be associated with subsequent changes in kidney function in a contemporary cohort of HIV+ and HIV-uninfected (HIV-) men.

METHODS

In the Multicenter AIDS Cohort Study, we measured baseline urine concentrations of 5 biomarkers from 2009 to 2011 in 860 HIV+ and 337 HIV- men: albumin, alpha-1-microglobulin (α1m), interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), and procollagen type III N-terminal propeptide (PIIINP). We evaluated associations of urine biomarker concentrations with annual changes in estimated glomerular filtration rate (eGFR) using multivariable linear mixed models adjusted for demographics, traditional kidney disease risk factors, HIV-related risk factors, and baseline eGFR.

RESULTS

Over a median follow-up of 4.8 years, the average annual eGFR decline was 1.42 mL/min/1.73 m2/year in HIV+ men and 1.22 mL/min/1.73 m2/year in HIV- men. Among HIV+ men, the highest vs. lowest tertiles of albumin (-1.78 mL/min/1.73 m2/year, 95% CI -3.47 to -0.09) and α1m (-2.43 mL/min/1.73 m2/year, 95% CI -4.14 to -0.73) were each associated with faster annual eGFR declines after multivariable adjustment. Among HIV- men, the highest vs. lowest tertile of α1m (-2.49 mL/min/1.73 m2/year, 95% CI -4.48 to -0.50) was independently associated with faster annual eGFR decline. Urine IL-18, KIM-1, and PIIINP showed no independent associations with eGFR decline, regardless of HIV serostatus.

CONCLUSIONS

Among HIV+ men, higher urine albumin and α1m are associated with subsequent declines in kidney function, independent of eGFR.

摘要

背景

HIV 感染者(HIV+)发生慢性肾脏病的风险增加,但血清肌酐不能检测到早期肾功能丧失。我们假设尿液肾损伤生物标志物与 HIV+和 HIV-(HIV-)男性的后续肾功能变化有关。

方法

在多中心艾滋病队列研究中,我们在 2009 年至 2011 年间测量了 860 名 HIV+和 337 名 HIV-男性的尿液中 5 种生物标志物的基线浓度:白蛋白、α1-微球蛋白(α1m)、白细胞介素 18(IL-18)、肾损伤分子 1(KIM-1)和前胶原 III N 端前肽(PIIINP)。我们使用多变量线性混合模型评估了尿液生物标志物浓度与估计肾小球滤过率(eGFR)年度变化的关系,该模型调整了人口统计学、传统肾脏疾病危险因素、HIV 相关危险因素和基线 eGFR。

结果

在中位随访 4.8 年期间,HIV+男性的平均每年 eGFR 下降 1.42mL/min/1.73m2/year,HIV-男性的平均每年 eGFR 下降 1.22mL/min/1.73m2/year。在 HIV+男性中,白蛋白(-1.78mL/min/1.73m2/year,95%CI-3.47 至-0.09)和 α1m(-2.43mL/min/1.73m2/year,95%CI-4.14 至-0.73)的最高与最低三分位组之间,每年 eGFR 下降均与多变量调整后更快的 eGFR 下降相关。在 HIV-男性中,α1m 的最高与最低三分位组之间(-2.49mL/min/1.73m2/year,95%CI-4.48 至-0.50)的 eGFR 下降与独立相关。尿液白细胞介素 18、KIM-1 和 PIIINP 与 eGFR 下降无关,无论 HIV 血清状态如何。

结论

在 HIV+男性中,较高的尿液白蛋白和 α1m 与随后的肾功能下降有关,与 eGFR 无关。

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