Mediation analysis for TNF-α as a mediator between multiple metal exposure and kidney function

Area of Science:

• Environmental Health
• Toxicology
• Nephrology

Background:

• The link between metal mixtures and kidney function is known, but the mechanisms of metal toxicity remain unclear.
• Oxidative stress is a suspected contributor to metal-induced kidney damage.
• Tumor necrosis factor alpha (TNF-α) is a potential mediator in metal toxicity pathways.

Purpose of the Study:

• To investigate the association between blood metal levels (arsenic, cadmium, cobalt, copper, lead, zinc) and kidney function in adults.
• To explore the mediating role of TNF-α in the relationship between metal exposure and kidney function.

Main Methods:

• Recruited 421 adults for a health examination.
• Measured blood metal concentrations using inductively coupled plasma mass spectrometry.
• Employed linear regression and mediation analysis to assess associations between metals, TNF-α, and estimated glomerular filtration rate (eGFR).

Main Results:

• Elevated blood levels of arsenic (As), lead (Pb), and zinc (Zn) were significantly associated with reduced kidney function (eGFR).
• TNF-α significantly mediated the effects of cadmium (Cd), As, and Pb on kidney function, accounting for 41.7%, 38.8%, and 20.8% respectively.
• TNF-α also mediated the impact of essential elements like cobalt (Co), copper (Cu), and Zn on kidney function.

Conclusions:

• TNF-α plays a significant role in mediating the adverse effects of metal mixtures on kidney function.
• Inflammation and kidney injury are suggested underlying mechanisms for metal exposure toxicity.
• Further research is needed to elucidate the precise biochemical mechanisms involved.