非肾脏疾病人群全氟化合物暴露与肾小球滤过率的关联分析

Associations between exposure to perfluoroalkyl substances and estimated glomerular filtration rate in population without kidney disease

  • 摘要:
    背景 全氟化合物(PFASs)是一种持久性有机污染物,在各地区人群生物样本中广泛检出。PFASs暴露与肾小球滤过率(eGFR)的关联研究结果不一致,且很少有研究探讨非肾脏疾病人群PFASs暴露对eGFR的影响。
    目的 探索非肾脏疾病人群PFASs暴露与eGFR和肾功能异常之间的关系。
    方法 2021年4月—2022年3月在中国天津两家医院按年龄和性别匹配(1∶1)随机从医院内分泌科和体检中心招募了609名eGFR>60 mL·min−1·1.73 m−2且无肾脏损害的参与者。通过问卷收集研究对象的性别、年龄、身高、体重、既往史、吸烟状况和饮酒情况等基本信息。从医院病历系统抄录空腹血糖(FBG)、肌酐(Cre)、总胆固醇(TC)、甘油三酯(TG)等生化指标。由专业人员使用标准方法测量了每位参与者的收缩压(SBP)和舒张压(DBP)。使用液相色谱串联质谱仪测定血清中PFASs暴露水平。采用多元线性回归和logistic回归评估研究人群PFASs暴露与eGFR和肾功能异常的关系。同时对年龄和性别进行亚组分析,探讨性别和年龄在PFASs暴露与eGFR关系中是否存在潜在的交互作用。
    结果 研究对象中男性283名,占总人数的46.5%。参与者的平均年龄为(56.86±12.47)岁,体重指数(BMI)为(25.59±3.84)kg·m−2。全氟辛酸(PFOA)、全氟己烷磺酸(PFHxS)、全氟辛烷磺酸(PFOS)、全氟壬酸(PFNA)、全氟癸酸(PFDA)、全氟十一烷酸(PFUnDA)、1H,1H,2H,2H-全氟-1-辛烷磺酸钠(6:2 FTS)、全氟戊烷磺酸(PFPeS)的检出率均大于75%,中位浓度分别为9.50、1.67、17.22、1.86、1.41、0.78、0.42、0.43 μg·L−1。调整性别、年龄、BMI、高血压、糖尿病、TC、TG、吸烟、饮酒的多元线性回归模型显示对数转换的PFHxS浓度和eGFR呈现负相关(b=−1.160,95%CI:−2.280~−0.410)。与最低三分位浓度相比,PFHxS最高三分位浓度组eGFR降低(b=−2.471,95%CI:−4.574~−0.368)。与男性相比,女性PFHxS水平与eGFR之间的负向关联更强(女性,b=−1.281,95%CI:−2.388~−0.174;男性,b=−0.781,95%CI:−2.823~1.261,P交互=0.043)。
    结论 非肾脏疾病人群中,血清PFHxS暴露水平与eGFR之间呈负相关关系,这种负向关联在女性中更为显著。

     

    Abstract:
    Background Perfluoroalkyl substances (PFASs) are classified as persistent organic pollutants and have been widely detected in human. Studies investigating the associations between PFASs exposure and estimated glomerular filtration rate (eGFR) yielded inconsistent results, and little is known about the effects of PFASs on eGFR in population without kidney disease.
    Objective To explore the associations of exposure to PFASs with eGFR and renal dysfunction in population without kidney disease.
    Methods A total of 609 participants with an eGFR > 60 mL·min−1·1.73 m−2 and without renal impairment matched for sex and age (1∶1) were recruited from endocrinology department and medical examination center of two hospitals in Tianjin, China, from April 2021 to March 2022. Each subject was interviewed using a structured questionnaire to collect information about sex, age, height, weight, disease history, smoking, alcohol intake, etc. Clinical parameters were obtained from medical record, such as fasting blood glucose (FBG), creatinine (Cre), total cholesterol (TC), and triglyceride (TG). Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured by professionals using standard methods. The serum concentrations of PFASs were determined by liquid chromatography/mass spectrometry. Multivariable linear and logistic regression models were performed to evaluate the associations of PFASs exposure with eGFR and renal dysfunction, respectively. Subgroup analyses stratified by age and sex were also performed to assess the modified effects of covariates on the associations of PFASs exposure with eGFR.
    Results There were 283 males, accounting for 46.5% of the total population. The mean age of the participants was (56.86±12.47) years, and the average body mass index (BMI) was (25.59±3.84) kg·m−2. Perfluoro-n-octanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluoro-n-nonanoic acid (PFNA), perfluoro-n-decanoic acid (PFDA), perfluoro-n-undecanoic acid (PFUnDA), sodium 1H, 1H, 2H, 2H-perfluoro-1-octanesulfonate (6:2 FTS), and perfluoropentane sulfonic acid (PFPeS) were positive in more than 75% of serum samples, and the corresponding median concentrations were 9.50, 1.67, 17.22, 1.86, 1.41, 0.78, 0.42, and 0.43 μg·L−1, respectively. After full adjustments of sex, age, BMI, hypertension, diabetes, TC, TG, smoking, and drinking, the linear regression models showed that log2-transformed PFHxS concentration was negatively associated with eGFR (b=−1.160, 95%CI: −2.280, −0.410). Compared with the lowest exposure tertile, the estimated change of eGFR in the highest tertile for PFHxS was significantly decreased (b=−2.471, 95%CI: −4.574, −0.368). Furthermore, compared with males, the negative association of PFHxS with eGFR was strengthened among females (female: b=−1.281, 95%CI: −2.388, −0.174; male: b=−0.781, 95%CI: −2.823, 1.261, Pinteraction=0.043).
    Conclusion A significant negative association between serum PFHxS and eGFR is observed in the sampled population without kidney disease, and females are more susceptible to PFASs exposure than the males.

     

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