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

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.