Department of Nephrology, Chang Gung Memorial Hospital, Keelung Branch, 222, Mai-Chin Road, Keelung 20401, Taiwan, ROC; College of Medicine, Chang Gung University, Taipei, Taiwan, No. 259, Wenhua 1st Rd., Guishan Dist., Taoyuan City 33302, Taiwan, ROC.
College of Medicine, Chang Gung University, Taipei, Taiwan, No. 259, Wenhua 1st Rd., Guishan Dist., Taoyuan City 33302, Taiwan, ROC; Department of Nephrology, Chang Gung Memorial Hospital, Linkou Branch, No. 5, Fuxing St., Guishan Dist., Taoyuan City 333423, Taiwan, ROC.
Environ Int. 2021 Oct;155:106585. doi: 10.1016/j.envint.2021.106585. Epub 2021 Apr 25.
Chronic kidney disease (CKD) is a growing concern worldwide. Exposure to xenoestrogens (XEs), such as phthalates, parabens, and phenols, lead to CKD. However, kidney function and its complex relationship with XEs, lifestyle, and dietary habits are not well understood.
In the present cross-sectional community-based cohort study, we enrolled 887 subjects for a questionnaire-based interview and laboratory tests. XE exposure concerning lifestyle/dietary habits were evaluated using questionnaires. Urinary levels of 17XE metabolites were measured in 60 subjects with high exposure risk scores and 60 subjects with low exposure risk scores.
Univariate and multivariate linear regression showed that a high exposure score (β ± SE: 4.226 ± 1.830, P = 0.021) was independently negatively associated with eGFR in 887 subjects. Univariate and multivariate linear regression to urinary XEs and urine albumin creatinine excretion ratio (UACR) in 120 subjects indicated that ethylparaben (EP) (β: 1.934, 95% CI: 0.135-3.733, P = 0.035) was significantly associated with increased UACR. Multivariate regression analyses of the CKD subgroup (n = 38), after adjusting for age, showed that higher levels of mono-(2-ethylhexyl) phthalate (MEHP), EP, nonylphenol (NP), and benzophenone-3 (BP-3) were significantly associated with lower estimated glomerular filtration rate (eGFR). Higher urinary levels of MEHP (OR: 3.037, 95% CI: 1.274-7.241) were more likely associated with high exposure scores (>5 points), after adjusting for diabetes, gender, eGFR, age, Na, Ca, albumin, vitamin D, systolic blood pressure (SBP), white blood cell count, total bilirubin, aspartate transaminase, and heart rate. MEHP (β ± SE: 0.033 ± 0.009, P < 0.001) was also significantly positively associated with total exposure scores after applying multivariate linear regression analyses.
XE exposure scores obtained from the questionnaires were negatively associated with kidney function. Urinary metabolites of XEs, including EP, NP, BP-3, and MEHP, are potential risk factors for microalbuminuria and decline in kidney function. MEHP seemed to have the strongest correlation with high exposure scores and decline in kidney function.
慢性肾病(CKD)是全球日益关注的问题。接触外源性雌激素(XEs),如邻苯二甲酸酯、对羟基苯甲酸酯和酚类物质,会导致 CKD。然而,肾脏功能及其与 XEs、生活方式和饮食习惯的复杂关系尚未得到充分理解。
在本项基于社区的横断面队列研究中,我们招募了 887 名受试者进行基于问卷的访谈和实验室检查。使用问卷评估与生活方式/饮食习惯有关的 XE 暴露情况。在 60 名高暴露风险评分和 60 名低暴露风险评分的受试者中测量了 17 种 XE 代谢物的尿液水平。
单变量和多变量线性回归显示,在 887 名受试者中,高暴露评分(β±SE:4.226±1.830,P=0.021)与 eGFR 呈负相关。对 120 名受试者的尿液 XE 和尿白蛋白肌酐排泄率(UACR)进行单变量和多变量线性回归分析表明,乙基对羟基苯甲酸酯(EP)(β:1.934,95%CI:0.135-3.733,P=0.035)与 UACR 升高显著相关。在调整年龄后,对 CKD 亚组(n=38)进行多变量回归分析显示,较高水平的单(2-乙基己基)邻苯二甲酸酯(MEHP)、EP、壬基酚(NP)和二苯甲酮-3(BP-3)与估算肾小球滤过率(eGFR)降低显著相关。经糖尿病、性别、eGFR、年龄、Na、Ca、白蛋白、维生素 D、收缩压(SBP)、白细胞计数、总胆红素、天门冬氨酸转氨酶和心率调整后,MEHP 尿水平(OR:3.037,95%CI:1.274-7.241)与高暴露评分(>5 分)的相关性更高。经多变量线性回归分析,MEHP(β±SE:0.033±0.009,P<0.001)与总暴露评分也呈显著正相关。
从问卷中获得的 XE 暴露评分与肾功能呈负相关。尿液 XE 代谢物,包括 EP、NP、BP-3 和 MEHP,是微量白蛋白尿和肾功能下降的潜在危险因素。MEHP 似乎与高暴露评分和肾功能下降相关性最强。