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<p>Environmental heavy metals are recognized nephrotoxicants, yet evidence on their combined effects on adolescent kidney function remains limited. Most prior analyses have treated exposures as static and independent, overlooking how metal–metal interactions may shift across different renal health states. In this study, we examined whether urinary metal co-exposure networks differ by levels of kidney function markers and identified key pairs undergoing network rewiring. We analyzed U.S. adolescents aged 12–19 years from the National Health and Nutrition Examination Survey (2009–2018), focusing on 11 urinary metals: arsenic, cobalt, antimony, cesium, thallium, molybdenum, lead, cadmium, mercury, tungsten, and uranium. Four renal biomarkers were evaluated: estimated glomerular filtration rate, blood urea nitrogen, serum uric acid, and albumin-to-creatinine ratio. For each biomarker, participants were stratified into lower- and higher-risk groups, and partial correlation networks of metal–metal pairs were constructed. Differential network analysis identified three rewiring patterns: disappearance (loss of correlation), emergence (new correlation), and differential-strength (change in correlation magnitude). Three metal pairs—arsenic–cobalt, arsenic–antimony, and cesium–thallium—consistently exhibited network rewiring across all biomarkers, suggesting robust associations with renal health transitions. Distinct interaction profiles were observed for each biomarker, and sex-stratified analyses showed greater network shifts in males than females, particularly involving molybdenum–lead and cobalt–molybdenum. These findings indicate that adolescent kidney function is linked not only to individual metal levels but also to dynamic changes in co-exposure structures. This study provides the first systems-level application of differential network analysis to environmental metals in youth, highlighting the need for sex-specific and interaction-aware approaches in nephrotoxicity research.</p>

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Differential Network Analysis of Environmental Metal Co-exposures and Kidney Health in Adolescents Aged 12–19

  • 期刊论文

  • 发表日期：

    2025年11月6日

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  • Yujie Weng,
  • Jie Xing,
  • Ling Zhang,
  • Ying Zhang,
  • Zhi Wang,
  • Xu Steven Xu,
  • Min Yuan,
  • Fangbiao Tao

摘要

Environmental heavy metals are recognized nephrotoxicants, yet evidence on their combined effects on adolescent kidney function remains limited. Most prior analyses have treated exposures as static and independent, overlooking how metal–metal interactions may shift across different renal health states. In this study, we examined whether urinary metal co-exposure networks differ by levels of kidney function markers and identified key pairs undergoing network rewiring. We analyzed U.S. adolescents aged 12–19 years from the National Health and Nutrition Examination Survey (2009–2018), focusing on 11 urinary metals: arsenic, cobalt, antimony, cesium, thallium, molybdenum, lead, cadmium, mercury, tungsten, and uranium. Four renal biomarkers were evaluated: estimated glomerular filtration rate, blood urea nitrogen, serum uric acid, and albumin-to-creatinine ratio. For each biomarker, participants were stratified into lower- and higher-risk groups, and partial correlation networks of metal–metal pairs were constructed. Differential network analysis identified three rewiring patterns: disappearance (loss of correlation), emergence (new correlation), and differential-strength (change in correlation magnitude). Three metal pairs—arsenic–cobalt, arsenic–antimony, and cesium–thallium—consistently exhibited network rewiring across all biomarkers, suggesting robust associations with renal health transitions. Distinct interaction profiles were observed for each biomarker, and sex-stratified analyses showed greater network shifts in males than females, particularly involving molybdenum–lead and cobalt–molybdenum. These findings indicate that adolescent kidney function is linked not only to individual metal levels but also to dynamic changes in co-exposure structures. This study provides the first systems-level application of differential network analysis to environmental metals in youth, highlighting the need for sex-specific and interaction-aware approaches in nephrotoxicity research.