Abstract
BACKGROUND: Chronic kidney disease (CKD) is a global public health issue. Heavy metals and trace elements may influence kidney function. This study aimed to investigate the association between plasma concentrations of 24 heavy metals and trace elements and kidney function, including estimated glomerular filtration rate (eGFR) and CKD status in European adults. METHODS: This study included adult participants from the Swiss Kidney Project on Genes in Hypertension cohort (2008-2013). Associations with eGFR and CKD were assessed using multivariable linear and logistic regression, and restricted cubic spline models for non-linear trends. Mixture effects were evaluated using least absolute shrinkage and selection operator for variable selection, followed by weighted quantile sum (WQS) regression. Multiple sensitivity analyses were conducted to assess robustness. RESULTS: Of the 988 participants (mean age 47.0 years, 52.3% female), 72 (7.3%) had CKD. In multivariable linear models with continuous exposures, higher plasma tin, antimony and iodine were associated with lower eGFR, but none remained significant after false discovery rate (FDR) correction. In quartile analyses, lower eGFR was observed in the highest exposure quartile for zinc and thallium, with a borderline trend for iodine. Arsenic showed a significant non-linear relationship with eGFR, with a turning point at ≈11.7 μg/l and an estimated decline of 3.27 ml/min/1.73 m(2) from the 25th percentile. For CKD, elevated levels of molybdenum, copper and iodine were linked to higher odds, whereas aluminum and silver were inversely associated. After FDR correction, only molybdenum remained significant. WQS regression indicated that tin, antimony, iodine, molybdenum and cadmium contributed most to lower eGFR, while iodine, arsenic, palladium, manganese and copper showed the strongest associations with CKD. CONCLUSIONS: After FDR adjustment across 24 elements, no individual element remained associated with eGFR, whereas molybdenum remained linked to CKD. Findings involving iodine were nominal and should be considered exploratory. Longitudinal and mechanistic studies are needed to validate these observations and clarify causality.