Sheela Sathyanarayana1, Joseph T Flynn2, Mary Jo Messito3, Rachel Gross3, Kathryn B Whitlock4, Kurunthachalam Kannan5, Rajendiran Karthikraj5, Debra Morrison6, Maryann Huie3, Dimitri Christakis7, Leonardo Trasande8. 1. 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. Electronic address: sheela.sathyanarayana@seattlechildrens.org. 2. Department of Pediatrics, Division of Nephrology, University of Washington, Seattle, WA, USA. 3. Department of Pediatrics, New York University School of Medicine, New York, NY, USA. 4. Center for Child Health, Behavior and Development, Seattle Children's Research Institute, Seattle, WA, USA. 5. Department of Health, Wadsworth Center, New York State, NY, USA. 6. Feinstein Institute for Medical Research, Manhasset, NY, USA. 7. 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. 8. Department of Pediatrics, New York University School of Medicine, New York, NY, USA; NYU Wagner School of Public Service, New York, NY, USA; Department of Nutrition, Food, and Public Health, NYU Steinhardt School of Culture, Education and Human Development, New York, NY, USA; NYU Global Institute of Public Health, New York University, New York, NY, USA.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: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. METHODS: 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. RESULTS: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. CONCLUSIONS: 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.
Authors: Melissa M Melough; Drew B Day; Amanda M Fretts; Sarah Wang; Joseph T Flynn; Ian H de Boer; Hongkai Zhu; Kurunthachalam Kannan; Sheela Sathyanarayana Journal: Int J Environ Res Public Health Date: 2022-04-19 Impact factor: 4.614