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

PLoS One. 2024 Dec 17;19(12):e0315688. doi: 10.1371/journal.pone.0315688. eCollection 2024.

Abstract

Background: While the nephrotoxicity of lead and cadmium is well-established, the impact of low-level exposure on risk of chronic kidney disease (CKD) and long-term health outcomes, especially in CKD patients, remains unclear. This study examines the association between low-level lead and cadmium exposure with risks of CKD and long-term mortality.

Method: We analyzed data from adult participants of 2003-2012 National Health and Nutrition Examination Survey in the United States. CKD was defined as estimated glomerular filtration rate < 60 ml/min/1.73 m2. Elevated blood lead (≥ 1.5 μg/dL) and cadmium (≥ 0.4 μg/L) levels were assessed for their associations with CKD and all-cause mortality, with survival tracked until December 31, 2019.

Results: Among the 24,810 participants (mean age 44.4 years, 48.9% male), 1,309 (3.9%) had CKD. Lead and cadmium levels were significantly higher in participants with CKD compared to those without. Elevated lead (OR: 1.41, 95% CI: 1.15-1.74) and cadmium (OR: 1.23, 95% CI: 1.03-1.46) levels were both associated with increased CKD risk, with the highest risk in those with both lead ≥ 1.5 μg/dL and cadmium ≥ 0.4 μg/L (OR: 1.65, 95% CI 1.27-2.14). During a median follow-up of 141 months, 2,255 participants died (7.0 per 10,000 person-months). Elevated cadmium was associated with higher mortality risk in CKD (HR: 1.42, 95% CI: 1.07-1.88) and non-CKD populations (HR: 1.40, 95% CI: 1.24-1.58), while lead levels were not significantly associated with mortality in either group. Participants with both elevated lead and cadmium had a significantly higher mortality risk (HR: 1.32, 95% CI: 1.13-1.54).

Conclusion: Low-level cadmium and lead exposure are linked to increased CKD risk, with cadmium also associated with higher long-term mortality in both CKD and non-CKD populations. These findings highlight the need for public health efforts to reduce exposure and further research on long-term impacts.

MeSH terms

  • Adult
  • Cadmium* / adverse effects
  • Cadmium* / blood
  • Environmental Exposure* / adverse effects
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Lead* / adverse effects
  • Lead* / blood
  • Lead* / toxicity
  • Male
  • Metals, Heavy / adverse effects
  • Metals, Heavy / blood
  • Middle Aged
  • Nutrition Surveys*
  • Renal Insufficiency, Chronic* / blood
  • Renal Insufficiency, Chronic* / chemically induced
  • Renal Insufficiency, Chronic* / mortality
  • Risk Factors
  • United States / epidemiology

Substances

  • Cadmium
  • Lead
  • Metals, Heavy

Grants and funding

This study was funded by a grant from Chi Mei Medical Center to Ming-Yan Jiang [CMFHR112020]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.