State Key Laboratory of Environment Health (Incubation), Key Laboratory of Environment and Health, Ministry of Education, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, #13 Hangkong Road, Wuhan, Hubei, 430030, China.
Health Management Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Int J Hyg Environ Health. 2024 Aug;261:114424. doi: 10.1016/j.ijheh.2024.114424. Epub 2024 Jul 16.
Exposure to environmental contaminants and the development of hypertension and diabetes represent crucial risk factors for chronic kidney disease (CKD). Toxicological studies have revealed that organophosphate esters (OPEs) impair kidney function. However, the joint effects of OPE exposure on kidney injury and the interactions of OPE exposure with hypertension or diabetes on kidney injury remain unclear. Our study aimed to investigate the individual and joint effects of OPE exposure on renal injury, as well as the potential interaction between OPE exposure and hypertension or diabetes on kidney injury. The study enrolled 1938 participants from Wuhan, China. To explore the relationship between OPE exposure and renal injury, we conducted multivariate linear and logistic regression analysis. The results indicated that each unit increase in 4-hydroxyphenyl diphenyl phosphate (4-HO-DPHP), bis(2-butoxyethyl) phosphate (BBOEP), and tris(2-chloroethyl) phosphate (TCEP) (1 μg/L-ln transformed) was associated with a decreased 0.57 mL/min/1.73 m (95%CI: -1.05, -0.09), 0.85 mL/min/1.73 m (95%CI: -1.52, -0.19) and 1.24 mL/min/1.73 m (95%CI: -2.26, -0.23) of estimated glomerular filtration rate (eGFR), while each unit increase in 4-HO-DPHP and BBOEP (1 μg/L-ln transformed) was associated with 14% and 20% elevation of incident impaired renal function (IRF) risk. Notably the highest tertile of BCIPHIPP was positively associated with eGFR, although the p for trend ＞ 0.05. We employed Bayesian kernel machine regression (BKMR) and quartile-based g-computation (qgcomp) models to explore the joint effects of OPE mixtures on eGFR and IRF. Both the results of BKMR and qgcomp model consistently demonstrated negative associations between OPE mixtures and eGFR, and TCEP and 4-HO-DPHP were major contributors. Furthermore, we observed multiplicative interactions of diphenyl phosphate (DPHP), BBOEP, di-ocresyl phosphate (DoCP) & di-p-cresyl phosphate (DpCP), 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP) and hypertension or diabetes on kidney injury (all P＜0.05). Those with diabetes or hypertension and higher OPE metabolite concentrations had increased risk of kidney function impairment compared to those who did not have diabetes or hypertension. These findings suggest that specific OPE exposure may elevate the risk of renal injury, particularly among hypertensive and diabetic populations.
暴露于环境污染物以及高血压和糖尿病的发展是慢性肾脏病（CKD）的重要危险因素。毒理学研究表明，有机磷酸酯（OPEs）会损害肾功能。然而，OPE 暴露对肾脏损伤的单独和联合作用，以及 OPE 暴露与高血压或糖尿病对肾脏损伤的相互作用仍不清楚。我们的研究旨在探讨 OPE 暴露对肾脏损伤的单独和联合作用，以及 OPE 暴露与高血压或糖尿病对肾脏损伤的潜在相互作用。该研究纳入了来自中国武汉的 1938 名参与者。为了探讨 OPE 暴露与肾脏损伤之间的关系，我们进行了多变量线性和逻辑回归分析。结果表明，每增加 4-羟基二苯磷酸（4-HO-DPHP）、双（2-丁氧基乙基）磷酸酯（BBOEP）和三（2-氯乙基）磷酸酯（TCEP）（1μg/L-ln 转换）1 个单位，估计肾小球滤过率（eGFR）分别降低 0.57mL/min/1.73m（95%CI：-1.05，-0.09）、0.85mL/min/1.73m（95%CI：-1.52，-0.19）和 1.24mL/min/1.73m（95%CI：-2.26，-0.23），而 4-HO-DPHP 和 BBOEP（1μg/L-ln 转换）每增加一个单位，患肾脏功能障碍（IRF）的风险就会增加 14%和 20%。值得注意的是，BCIPHIPP 的最高三分位与 eGFR 呈正相关，尽管趋势检验的 p 值＞0.05。我们采用贝叶斯核机器回归（BKMR）和四分位数基于 g 计算（qgcomp）模型来探讨 OPE 混合物对 eGFR 和 IRF 的联合作用。BKMR 和 qgcomp 模型的结果均一致表明，OPE 混合物与 eGFR 之间存在负相关，TCEP 和 4-HO-DPHP 是主要贡献者。此外，我们观察到二苯基磷酸（DPHP）、BBOEP、二邻甲苯基磷酸（DoCP）&二对甲苯基磷酸（DpCP）、1-羟基-2-丙基双（1-氯-2-丙基）磷酸酯（BCIPHIPP）与高血压或糖尿病对肾脏损伤的相乘交互作用（均 P＜0.05）。与没有高血压或糖尿病的人相比，患有糖尿病或高血压且 OPE 代谢物浓度较高的人肾脏功能障碍的风险增加。这些发现表明，特定的 OPE 暴露可能会增加肾脏损伤的风险，尤其是在高血压和糖尿病患者中。
