Association of low-level heavy metal exposure with risk of chronic kidney disease and long-term mortality Original paper

What was studied?

This study investigated the association between low-level heavy metal exposure—specifically lead and cadmium—and chronic kidney disease (CKD) risk and long-term mortality, emphasizing how “low-level heavy metal exposure” may influence renal dysfunction and survival outcomes. Using 2003–2012 NHANES data with mortality follow-up through 2019, the researchers examined whether blood lead ≥1.5 μg/dL and blood cadmium ≥0.4 μg/L, both below established toxicity thresholds, were linked to CKD and all-cause mortality. The analysis incorporated demographic, metabolic, cardiovascular, behavioral, and sociodemographic covariates. CKD was defined by an estimated glomerular filtration rate (eGFR) <60 ml min 1.73 m², and albuminuria analyses were added to mitigate reverse causality. mortality associations evaluated using cox regression models in ckd non-ckd subgroups. figures illustrate survival curves, showing steeper declines groups with elevated cadmium, details fully adjusted hazard ratios confirming cadmium’s strong signal.< p>

Who was studied?

The cohort included 24,810 adults from a nationally representative U.S. sample, with a mean age of 44.4 years and a near-even sex distribution. According to Table 1 (page 5), 39% had elevated blood lead and 40.3% had elevated cadmium levels. Individuals with higher metal levels were more likely to be older, have lower socioeconomic status, smoke, and exhibit higher rates of hypertension, cardiovascular disease, and stroke. CKD prevalence was 3.9%, representing 1,309 participants. The sample’s diversity—69.3% White, 11.1% Black, 13.4% Hispanic—supports the generalizability of findings. Cross-sectional and longitudinal components enabled evaluation of both CKD risk and long-term mortality across demographic strata.

Most important findings

Low-level exposure to lead and cadmium was clearly associated with clinically relevant kidney and mortality outcomes. Participants with CKD had significantly higher mean blood lead (2.14 vs. 1.58 μg/dL) and cadmium (0.60 vs. 0.53 μg/L). After adjustment, lead ≥1.5 μg/dL (OR 1.41) and cadmium ≥0.4 μg/L (OR 1.23) independently increased CKD odds. Albuminuria analyses confirmed dose-dependent associations even in those with normal eGFR. Mortality analyses demonstrated that elevated cadmium increased risk in both CKD (HR 1.42) and non-CKD (HR 1.40) populations, while lead was not independently predictive. Still, the combined elevation of both metals produced a synergistic mortality effect (HR 1.32). Microbiome-relevant considerations arise from known heavy-metal-induced dysbiosis documented in other literature; while not directly measured here, cadmium and lead can shift gut microbial communities, promote oxidative stress, and disrupt barrier integrity, pathways relevant for microbiome signature databases.

Key implications

The findings indicate that even low-level heavy metal exposure negatively affects kidney health and survival, challenging current toxicity thresholds. Cadmium’s stronger mortality association suggests it is a critical environmental toxin requiring intensified surveillance and mitigation, especially among smokers and groups with socioeconomic vulnerabilities. Lead’s robust association with CKD reinforces the need for ongoing exposure reduction despite declining national levels. Co-exposure dramatically heightens mortality risk, signaling the importance of cumulative toxicant assessment rather than single-agent evaluation. Clinically, results support incorporating environmental exposure screening into CKD risk assessment and highlight potential relevance for microbiome research, given heavy metals’ documented ability to disrupt microbial ecology and metabolic pathways.

Citation

Kuo P-F, Huang Y-T, Chuang M-H, Jiang M-Y. Association of low-level heavy metal exposure with risk of chronic kidney disease and long-term mortality. PLoS One. 2024;19(12):e0315688. doi:10.1371/journal.pone.0315688