Environmental exposure to melamine and its derivatives and kidney outcomes in children

Drew B Day; Melissa M Melough; Joseph T Flynn; Hongkai Zhu; Kurunthachalam Kannan; John Ruzinski; Ian H de Boer; Sheela Sathyanarayana

doi:10.1016/j.envres.2024.118789

Environmental exposure to melamine and its derivatives and kidney outcomes in children

Environ Res. 2024 Mar 28;252(Pt 1):118789. doi: 10.1016/j.envres.2024.118789. Online ahead of print.

Authors

Drew B Day¹, Melissa M Melough², Joseph T Flynn³, Hongkai Zhu⁴, Kurunthachalam Kannan⁵, John Ruzinski⁶, Ian H de Boer⁷, Sheela Sathyanarayana⁸

Affiliations

¹ Center for Child Health, Behavior, and Development, Seattle Children's Research Institute, 1920 Terry Ave, Seattle, WA, 98101, USA. Electronic address: drew.day@seattlechildrens.org.
² Department of Health Behavior and Nutrition Sciences, University of Delaware, Newark, DE, 19713, USA. Electronic address: melough@udel.edu.
³ Division of Nephrology, Seattle Children's Hospital, 4800 Sand Point NE, Seattle, WA, 98105, USA; Department of Pediatrics, University of Washington, 1959 Northeast Pacific Street, Seattle, WA, 98195, USA. Electronic address: joseph.flynn@seattlechildrens.org.
⁴ Department of Environmental Medicine, Nankai University, No. 38 Tongyan Road, Jinnan District, Tianjin, 300350, China. Electronic address: zhuhongkai@nankai.edu.cn.
⁵ Wadsworth Center, New York State Department of Health, Albany, NY 12237, USA. Electronic address: Kurunthachalam.kannan@health.ny.gov.
⁶ Kidney Research Institute, Department of Nephrology, University of Washington, 908 Jefferson St, Seattle, WA, 98104, USA. Electronic address: Jruzinski@Nephrology.washington.edu.
⁷ Kidney Research Institute, Department of Nephrology, University of Washington, 908 Jefferson St, Seattle, WA, 98104, USA. Electronic address: IdeBoer@Nephrology.washington.edu.
⁸ Center for Child Health, Behavior, and Development, Seattle Children's Research Institute, 1920 Terry Ave, Seattle, WA, 98101, USA; Department of Pediatrics, University of Washington, 1959 Northeast Pacific Street, Seattle, WA, 98195, USA. Electronic address: sheela.sathyanarayana@seattlechildrens.org.

PMID: 38555096
DOI: 10.1016/j.envres.2024.118789

Abstract

Melamine caused acute nephrotoxicity in a past food adulteration incident, but it is unclear whether and how widespread ambient exposure to melamine and related compounds might affect pediatric kidney health. We assessed cross-sectional associations between childhood exposure to melamine and its derivatives and biomarkers of kidney injury and health and explored potential heterogeneity by sex suggested by sex-dependent differences in renal physiology. We measured melamine and its derivatives ammeline, ammelide, and cyanuric acid (CYA) in spot urine samples collected from 192 children from an urban site (Seattle, WA) and 187 children from a rural site (Yakima, WA) aged 4-8 years in the Global Alliance to Prevent Prematurity and Stillbirth (GAPPS) Study. In addition, biomarkers of kidney injury were measured in the same urine samples, including albumin, total protein, KIM-1, NAG, NGAL, and EGF. We utilized linear regressions to examine associations between individual chemical exposures and kidney biomarkers. Interaction terms examined association modification by sex, as well as potential interactions between melamine and CYA. Despite comparable exposures, girls had higher levels of many kidney injury biomarkers compared to boys. A ten-fold higher melamine concentration was associated with a 18% (95% CI: 5.6%, 31%) higher EGF in the full sample, while ten-fold higher melamine was associated with a 76% (14.1%, 173%) higher KIM-1 in boys but not in girls (-10.1% (-40.6%, 36.1%), interaction p = 0.026). Melamine exhibited significant negative interactions with CYA in association with total protein and NAG that appeared to be specific to girls. Our results suggest possible associations between melamine exposure and markers of kidney injury that may be more pronounced in boys. These findings provide novel insights into melamine and related derivative compound health effects at low levels of exposure in children and emphasize the role of sex in mediating the relationship between nephrotoxicant exposure and kidney injury.

Keywords: Cyanuric acid; Emerging contaminants; Environmental epidemiology; Kidney; Melamine; Nephrotoxicity.

Grants and funding

UG3 OD023271/OD/NIH HHS/United States