Department of Environmental Health Sciences, School of Public Health, Seoul National University, Seoul, Republic of Korea.
Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of Korea.
Environ Int. 2019 Oct;131:105034. doi: 10.1016/j.envint.2019.105034. Epub 2019 Jul 30.
Organophosphate esters (OPEs) have been widely used in building materials and consumer products as flame retardants and plasticizers. In vitro studies have suggested adverse effects of OPEs on the kidney. Despite accumulating evidence indicating widespread exposure to OPEs, their association with renal function in humans has not been evaluated. This study aims to investigate the association between OPEs exposure and chronic kidney disease (CKD) among the general US adult population by employing data from the US National Health and Nutrition Examination Survey (NHANES) 2013-2014. Among 1578 adults who were not currently pregnant, the associations of the urinary OPE metabolites with two CKD-related parameters, i.e., estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR), and CKD were assessed. To account for urine dilution, in addition to conventional creatinine-adjustment, covariate-adjusted creatinine standardization, which controls for potential confounding by kidney function, was employed. Multi-pollutant models were also constructed to verify the associations observed in the models on individual OPE metabolites. The urinary bis(2-chloroethyl) phosphate (BCEP) level was negatively associated with eGFR only with the covariate-adjusted standardization method, but not with the conventional creatinine adjustment. In addition, both bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) and di-n-butyl phosphate (DNBP) were positively associated with the ACR, regardless of methods of urine dilution adjustment. These three compounds were also associated with CKD. Following adjusting urine dilution with the covariate-adjusted standardization method, the association became more evident. Moreover, similar results were observed in the secondary analysis with the multi-pollutant models. Among the US general population, several OPEs were identified as potential chemical determinants of CKD. Experimental studies are warranted to understand the potential mechanisms underlying this observation.
有机磷酸酯（OPEs）作为阻燃剂和增塑剂已广泛应用于建筑材料和消费品中。体外研究表明 OPEs 对肾脏有不良影响。尽管越来越多的证据表明 OPEs 广泛存在于人体中，但它们与肾功能之间的关联尚未得到评估。本研究旨在通过使用美国国家健康和营养检查调查（NHANES）2013-2014 年的数据，研究美国普通成年人群中 OPEs 暴露与慢性肾脏病（CKD）之间的关系。在 1578 名未怀孕的成年人中，评估了尿中 OPE 代谢物与两个 CKD 相关参数（即估计肾小球滤过率[eGFR]和白蛋白与肌酐比[ACR]）以及 CKD 的关联。为了考虑尿液稀释，除了常规肌酐调整外，还采用了协变量调整的肌酐标准化方法，该方法可控制肾功能潜在的混杂因素。还构建了多污染物模型来验证个体 OPE 代谢物模型中观察到的关联。只有采用协变量调整的标准化方法，尿液中的双（2-氯乙基）磷酸酯（BCEP）水平才与 eGFR 呈负相关，而与常规肌酐调整无关。此外，双（1,3-二氯-2-丙基）磷酸酯（BDCIPP）和二正丁基磷酸酯（DNBP）与 ACR 均呈正相关，无论尿液稀释调整方法如何。这三种化合物也与 CKD 相关。采用协变量调整的标准化方法调整尿液稀释后，关联更加明显。此外，在多污染物模型的二次分析中也观察到了类似的结果。在美国普通人群中，几种 OPEs 被确定为 CKD 的潜在化学决定因素。需要进行实验研究以了解这一观察结果背后的潜在机制。
