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Associations of exposure to melamine, cyanuric acid, phthalates with markers of early kidney impairment, and their interactions in US adults: analyses of NHANES 2003–2004 data

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Abstract 

Melamine (MEL), cyanuric acid (CYA), and phthalates have kidney toxicity, respectively. Still, no study has explored whether there is an interaction of co-exposure to MEL, CYA, and phthalates on early kidney impairment, including cystatin C (CYST), beta 2-microglobulin (β2-MG), albumin creatinine ratio (ACR), and estimated glomerular filtration rate (eGFR). Urine samples were collected from 333 adults in the National Health and Nutrition Examination Survey (NHANES) 2003–2004, and urinary MEL, CYA, and ten metabolites of phthalates were quantified. The multiple markers of early kidney impairment were also measured, including serum CYST, β2-MG, urinary ACR, and eGFR. Their associations were explored by multiple linear and multivariate logistic regression models. Meanwhile, the interactions of co-exposure to MEL, CYA, and phthalates on early kidney impairment were analyzed by Wilcoxon rank-sum test combined with the LSD test. In the multiple linear regression model, urinary concentrations of monobenzyl phthalate (MBzP), mono(3-carboxypropyl) phthalate (MCPP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), and mono(2-ethylhexyl) phthalate (MEHP) were positively associated with urinary ACR, serum β2-MG, and CYST, respectively. Urinary concentrations of MBzP and MCPP were negatively associated with eGFR. In the multivariate logistic regression model, increased urinary CYA concentration was the risk factor of CYST abnormality with an odds ratio (OR) (95% confidence interval, 95% CI) of 2.38 (1.01, 5.60) (P = 0.047) and increased urinary MBzP concentration was the risk factor of ACR abnormality with an OR of 2.59 (1.41, 4.75) (P = 0.002). The co-exposure to MEL, CYA, and four phthalate metabolites (MEHP, MBzP, MCPP, and MECPP) presented significantly interactive effects on the markers of early kidney impairment, respectively. There were the independent and interactive effects of exposure to MEL, CYA, and specific phthalate metabolites on early kidney impairment. Due to co-exposure to multiple environmental chemicals in our daily life, more attention should be paid to the health damage raised by the synergistic effects of environmental chemicals.

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Data availability

The data presented in this study are available on request from the corresponding author. The data are not publicly available due to the privacy of study participants.

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Funding

This study was funded by the Shanghai Municipal Health Commission (grant number: 20214Y0019) and the National Natural Science Foundation of China (grant number: 82003412, 82173520).

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  1. Shaojie Liu and Yifei Wang contributed equally to this work.

Authors and Affiliations

  1. School of Public Health, Key Lab of Public Health Safety of the Ministry of Education, Fudan University, Shanghai, 200032, China

    Shaojie Liu, Yifei Wang, Feifei Huang, Hangwei Wang, Ruoru Yang, Gengsheng He, Bo Chen & Ruihua Dong

  2. Chemical Laboratory, Jing’an District Center for Disease Control and Prevention, Shanghai, 200041, China

    Qifan Yang

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  1. Shaojie Liu
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Contributions

We would like to thank all the participants for their participation and kind assistance. SL, YW, FH, HW, RY, and RD contributed to the conception and study design; SL, YW, and QY contributed to the acquisition of data; SL and RD performed data analysis; SL, RD, and BC contributed to the interpretation of the data; SL, YW, and RD contributed to manuscript writing; and GH, RD, and BC critically revised the manuscript.

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Correspondence to Ruihua Dong.

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This study was approved by the NCHS Research Ethics Review Board (protocol #98–12).

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Liu, S., Wang, Y., Huang, F. et al. Associations of exposure to melamine, cyanuric acid, phthalates with markers of early kidney impairment, and their interactions in US adults: analyses of NHANES 2003–2004 data. Environ Sci Pollut Res 29, 79516–79528 (2022). https://doi.org/10.1007/s11356-022-21455-9

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