School of Public Health/ Key Laboratory of Public Health Safety of Ministry of Education/ Key Lab of Health Technology Assessment, National Health Commission of the People's Republic of China, Fudan University, No. 130 Dong'an Road, Shanghai 200032, China.
School of Public Health/ Key Laboratory of Public Health Safety of Ministry of Education/ Key Lab of Health Technology Assessment, National Health Commission of the People's Republic of China, Fudan University, No. 130 Dong'an Road, Shanghai 200032, China.
Environ Int. 2020 Aug;141:105815. doi: 10.1016/j.envint.2020.105815. Epub 2020 May 29.
Higher melamine exposure may increase the risk of kidney stone formation and kidney injury in infants, but little is known about the potential nephrotoxic effects of environmental low-dose melamine and its derivative exposure on kidney function of adults in the general population. Our objective was to assess associations between urinary concentrations of melamine and its derivative, cyanuric acid, and kidney function through analyzing the data from the National Health and Nutrition Examination Survey (NHANES) 2003-2004. Information on 298 participants aged ≥20 years was utilized. Urinary melamine and cyanuric acid levels were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) were calculated to reflect kidney function. Covariate-adjusted creatinine standardization concentrations accounting for sex, race, age, race/ethically, and body mass index, was employed to control potential confounding of kidney function. Multivariable linear regression models were conducted to estimate associations of covariate-adjusted creatinine standardization urinary melamine and cyanuric acid concentrations with eGFR and UACR. Log-binomial regression models were performed to estimate risks of impaired kidney function and hypertension associated with urinary melamine and cyanuric acid levels. The geometric mean values of urinary melamine and cyanuric acid concentrations were 1.51 μg/L [95% confidence interval (CI): 1.21 μg/L, 1.89 μg/L] and 5.86 μg/L (95% CI: 5.34 μg/L, 6.44 μg/L), respectively. The median value of estimated daily intake (EDI) for melamine was 0.06 (ranging from undetectable to 1.11) μg/kg body weight/day calculated by urinary concentration and creatinine excretion accounting for sex and body weight. Adults in the fourth quartile of melamine and cyanuric acid exposure had 0.142 mL/min/1.73 m (95% CI: -0.271, -0.014) and 0.106 mL/min/1.73 m (95% CI: -0.020, 0.006) lower eGFR for melamine and cyanuric acid, respectively, compared to participants in the first quartile of exposure with adjustment for potential confounders. To our best knowledge, this is the first study to report associations between melamine and its derivative and kidney function of the U.S. adults from NHANES 2003-2004. The suggestive evidence revealed that individuals with high melamine exposure had lower eGFR than those with low melamine exposure, although no significant association between melamine and cyanuric acid exposure and markers of kidney function was observed. These findings should be interpreted with caution regarding the possible reverse causality.
更高的三聚氰胺暴露可能会增加婴儿肾结石形成和肾脏损伤的风险，但对于环境低剂量三聚氰胺及其衍生物暴露对普通人群成年人肾功能的潜在肾毒性影响知之甚少。我们的目的是通过分析 2003-2004 年全国健康和营养检查调查（NHANES）的数据，评估尿中三聚氰胺及其衍生物氰尿酸与肾功能之间的关系。利用了年龄≥20 岁的 298 名参与者的信息。使用液相色谱-串联质谱（LC-MS/MS）测定尿中三聚氰胺和氰尿酸水平。估算肾小球滤过率（eGFR）和尿白蛋白/肌酐比（UACR）用于反映肾功能。采用性别、种族、年龄、种族/民族和体重指数校正的肌酐标准化浓度来控制肾功能的潜在混杂因素。采用多变量线性回归模型估计校正后的肌酐标准化尿三聚氰胺和氰尿酸浓度与 eGFR 和 UACR 的关系。采用对数二项式回归模型估计与尿三聚氰胺和氰尿酸水平相关的肾功能障碍和高血压的风险。尿中三聚氰胺和氰尿酸浓度的几何平均值分别为 1.51μg/L（95%置信区间：1.21μg/L，1.89μg/L）和 5.86μg/L（95%置信区间：5.34μg/L，6.44μg/L）。根据尿浓度和肌酐排泄，按性别和体重校正后，三聚氰胺的估计每日摄入量（EDI）中位数为 0.06（范围从不可检测到 1.11）μg/kg 体重/天。与暴露于三聚氰胺和氰尿酸第一四分位数的参与者相比，暴露于第四四分位数的参与者的 eGFR 分别低 0.142mL/min/1.73m（95%置信区间：-0.271，-0.014）和 0.106mL/min/1.73m（95%置信区间：-0.020，0.006）。据我们所知，这是第一项报告 2003-2004 年 NHANES 中美国成年人三聚氰胺及其衍生物与肾功能之间关系的研究。有证据表明，与低三聚氰胺暴露者相比，高三聚氰胺暴露者的 eGFR 较低，尽管三聚氰胺和氰尿酸暴露与肾功能标志物之间没有显著关联。这些发现对于可能的反向因果关系应谨慎解释。
