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Interaction between plasma matrix metalloproteinases and arsenic, cadmium, lead, and selenium on chronic kidney

Hsi-Hsien Chen1, Chih-Yin Wu2, Sheng-Lun Hsu2

  • 1Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Nephrology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan.

Ecotoxicology and Environmental Safety
|December 7, 2025
PubMed

Insights

High levels of matrix metalloproteinases (MMPs), specifically MMP2 and MMP9, are linked to chronic kidney disease (CKD). This study found that MMP2 interacts with metal exposures, significantly increasing CKD risk.

Area of Science:

  • Nephrology and Environmental Health Sciences
  • Biochemistry and Molecular Biology

Background:

  • Renal fibrosis, marked by excessive extracellular matrix (ECM) deposition, is a key feature of chronic kidney disease (CKD).
  • Matrix metalloproteinases (MMPs), including MMP2 and MMP9, are crucial in ECM remodeling and have been implicated in renal fibrosis.
  • Environmental exposures to metals and metalloids are associated with CKD and may modulate MMP expression.

Purpose of the Study:

  • To investigate the association of plasma MMP2 and MMP9 concentrations and their genetic polymorphisms with CKD.
  • To examine the interactions between MMP2/MMP9 and metal exposures (selenium, cadmium, lead, arsenic) in relation to CKD.
  • To determine if MMP2/MMP9 genotypes are associated with CKD risk.

Main Methods:

  • Enzyme-linked immunosorbent assays (ELISAs) were used to measure plasma MMP2 and MMP9 concentrations in 215 CKD patients and 389 controls.
  • Quantification of plasma selenium, blood cadmium and lead, and urinary arsenic levels.
  • Genotyping of common MMP2 and MMP9 polymorphisms and logistic regression analysis to assess associations and interactions.

Main Results:

  • Elevated plasma MMP2 and MMP9 concentrations were significantly associated with increased odds of CKD (ORs 12.45 and 3.77, respectively).
  • No significant associations were found between MMP2 or MMP9 genotypes and CKD.
  • Significant additive interactions were observed between high plasma MMP2 and various metal exposures (arsenic, cadmium, lead, selenium) and high MMP9, all increasing CKD risk. A significant multiplicative interaction was noted between high plasma MMP2 and blood lead.

Conclusions:

  • Elevated plasma MMP2 and MMP9 concentrations are independently associated with CKD.
  • Genetic polymorphisms in MMP2 and MMP9 were not directly associated with CKD in this cohort.
  • This study provides the first evidence of interactions between plasma MMP2 concentrations and metal exposures, which collectively enhance the risk of developing CKD.
Keywords:
Chronic kidney diseaseMMP2MMP9MetalloidsMetalsPolymorphism

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