Role of kidney function in mediating the relationship between heavy metal exposure and all-cause mortality in older adults

Heavy metal exposure has well-established health risks, but its impact on all-cause mortality through renal function remains unclear. This study used data from 1,342 participants aged≥60 years in the National Health and Nutrition Examination Survey (2005-2018). A cross-sectional design was employed, with heavy metal composite scores derived using least absolute shrinkage and selection operator regression. Multivariate Cox proportional hazards models assessed the relationship between heavy metal exposure and all-cause mortality, while mediation analysis evaluated the role of estimated glomerular filtration rate (eGFR). The average participant age was 69.4 years. Higher composite metal exposure scores (CMES) were associated with older age, higher smoking rates, and increased blood lead (Pb) and cadmium (Cd) levels. CMES was significantly associated with mortality (adjusted HR=1.75, 95% CI:1.04-2.96), with Kaplan-Meier curves showing lower survival in participants with higher CMES (p=0.02). Pb and Cd levels were independently associated with increased mortality risk. eGFR was negatively correlated with mortality (adjusted HR=0.98, 95% CI: 0.97-0.99) and mediated 23.7% of the CMES-mortality relationship. These findings suggest that heavy metal exposure increases mortality risk, partly through impaired renal function.