Center for Child Health, Behavior and Development, Seattle Children's Research Institute, Seattle, WA, USA; Department of Pediatrics, Division of General Pediatrics, University of Washington, Seattle, WA, USA; Department of Environmental and Occupational Health Sciences, Seattle, WA, USA.
Department of Pediatrics, Division of Nephrology, University of Washington, Seattle, WA, USA.
Environ Res. 2019 Apr;171:18-23. doi: 10.1016/j.envres.2018.10.038. Epub 2018 Nov 2.
Melamine and cyanuric acid, which are currently used in a variety of common consumer products and present in foods, have been implicated in the development of urolithiasis and acute kidney injury in Chinese children. To determine whether US children have measurable concentrations of these chemicals in their bodies and whether they are at greater risk of acute kidney injury, we measured melamine and cyanuric acid exposure in a cohort of US children and determined their relationship with markers of kidney injury.
We measured urinary melamine and cyanuric acid in a convenience sample of 109 children (4 months - 8 years) from Seattle, WA and New York City, NY using liquid chromatography with tandem mass spectrometry. We measured several urinary markers of kidney injury: fatty acid binding protein 3 (FABP3), kidney injury molecule 1 (KIM1), neutrophil gelatinase-associated lipocalin (NGAL) using Luminex xMAP methods, and urine urea was measured using standard laboratory methods. We described urinary melamine and cyanuric acid concentrations and assessed predictors of the exposures. We used multivariable linear regression to assess relationships between melamine/cyanuric acid and kidney injury markers in unadjusted and adjusted (creatinine, age, sex) analyses.
Melamine and cyanuric acid were above the limit of detection (LOD) in 78% and 95% of all samples, respectively. The mean concentrations (SD) for melamine and cyanuric acid were 27.4 ng/ml (141.9 ng/ml) and 35.3 ng/ml (42.4 ng/ml). In unadjusted analyses, we observed statistically significant increases in the percentages of FABP3 and KIM1 in relation to a one log unit change in melamine and cyanuric acid, respectively. In adjusted analyses, we observed a 55% (95% CI 0, 141) increase in KIM1 in relation to a one log unit increase in cyanuric acid.
US children have detectable concentrations of melamine and cyanuric acid in urine, and these concentrations are higher than those reported in children from other countries. This is a novel finding that improves upon previous exposure estimates using questionnaires only and suggests widespread exposure in the population. Cyanuric acid is associated with increased KIM 1 concentrations, suggesting kidney injury. Given the potential widespread exposure, future analyses should examine melamine and cyanuric acid in relation to chronic kidney disease and markers of kidney injury in a larger cohort that is representative of the general population.
三聚氰胺和三聚氰酸目前被广泛应用于各种常见的消费产品中，也存在于食品中，已被证实与中国儿童尿路结石和急性肾损伤的形成有关。为了确定美国儿童体内是否存在这些化学物质的可测量浓度，以及他们是否有更高的急性肾损伤风险，我们对西雅图和纽约市的 109 名儿童（4 个月至 8 岁）进行了三聚氰胺和三聚氰酸暴露的检测，并确定了它们与肾损伤标志物的关系。
我们使用液相色谱-串联质谱法对来自华盛顿州西雅图和纽约市的 109 名儿童（4 个月-8 岁）的尿液样本进行了三聚氰胺和三聚氰酸的检测。我们使用 Luminex xMAP 方法检测了几种尿液肾损伤标志物：脂肪酸结合蛋白 3（FABP3）、肾损伤分子 1（KIM1）和中性粒细胞明胶酶相关脂质运载蛋白（NGAL），并使用标准实验室方法检测了尿尿素。我们描述了尿液中三聚氰胺和三聚氰酸的浓度，并评估了暴露的预测因素。我们使用多变量线性回归分析在未调整和调整（肌酐、年龄、性别）分析中评估了三聚氰胺/三聚氰酸与肾损伤标志物之间的关系。
在所有样本中，三聚氰胺和三聚氰酸的浓度分别有 78%和 95%超过了检测限（LOD）。三聚氰胺和三聚氰酸的平均浓度（SD）分别为 27.4ng/ml（141.9ng/ml）和 35.3ng/ml（42.4ng/ml）。在未调整的分析中，我们观察到三聚氰胺和三聚氰酸各增加一个对数单位，FABP3 和 KIM1 的百分比分别有统计学意义的增加。在调整分析中，我们观察到与三聚氰酸增加一个对数单位相关的 KIM1 增加了 55%（95%可信区间 0，141）。
美国儿童尿液中可检测到三聚氰胺和三聚氰酸的浓度，且这些浓度高于其他国家儿童的报告浓度。这是一个新的发现，它改进了之前仅使用问卷调查的暴露估计，表明在人群中存在广泛的暴露。三聚氰酸与 KIM1 浓度的增加有关，提示存在肾损伤。鉴于潜在的广泛暴露，未来的分析应该在一个更具代表性的一般人群的更大队列中，研究三聚氰胺和三聚氰酸与慢性肾脏病和肾损伤标志物的关系。
