Mediation Effect of Oxidative Stress in the Associations between Cadmium Exposure and Renal Tubular Damage of Residents in Metal-Polluted Regions in Korea

Cadmium (Cd) exposure has been reported to cause renal tubular damage (RTD) and oxidative stress (OS), and associations between OS and RTD have already been reported. However, the mediating role of OS in the association between urinary Cd and RTD has not been examined in an epidemiological study. This cross-sectional study aimed to examine the association between Cd exposure and RTD, with a focus on whether OS acts as a mediating factor, particularly among residents of metal-polluted regions. This study was conducted in the vicinity of two refineries in the Republic of Korea. A total of 243 participants were recruited from the Forensic Research via Omics Markers (FROM) study, targeting individuals who had lived in the areas for over ten years. Spot urine samples were collected and analyzed for urinary Cd, OS markers (8-hydroxy-2′-deoxyguanosine [8-OHdG] and malondialdehyde [MDA]), and RTD markers (beta-2-microglobulin [β2-MG] and N-acetyl-β-d-glucosaminidase [NAG]). Multivariate regression was employed to assess the dose-response relationships between Cd and RTD, Cd and OS, and OS and RTD. Mediation analysis was conducted to determine the mediating role of OS in the Cd-RTD relationship. Significant dose-response relationships were observed between Cd and RTD, Cd and OS, and OS and RTD. Furthermore, 8-OHdG showed significant mediating effects on the association between Cd and β2-MG, and MDA mediated associations between Cd and both β2-MG and NAG. These findings underscore the critical role of OS in the pathway from Cd exposure to RTD, offering insight into potential targets for appropriate interventions and the prevention of Cd-induced renal toxicity.