Associations of serum lithium, nickel, cobalt, and manganese with chronic kidney disease among Chinese older adults: Mediating role of lipid metabolism and moderating effect of lifestyle.

Lithium (Li), nickel (Ni), cobalt (Co), and manganese (Mn) are widely distributed environmental metals and are also important constituent elements of Li-ion batteries. However, the potential health effects of mixed exposure to these metals in older adults remain unclear. This preliminary cross-sectional study investigated the associations between serum Li, Ni, Co, and Mn concentrations and CKD risk, assessed Li/Ni/Co/Mn (LNCM) mixture effects, assessed the effects of Li/Ni/Co/Mn (LNCM) mixture exposure, explored potential pathways, and evaluated the moderating role of healthy lifestyle behaviors. In a cross-sectional study of 844 community-dwelling older adults in Wuhan, China, serum Li, Ni, Co, and Mn were measured using ICP-MS. Logistic regression, weighted quantile sum (WQS) regression, Bayesian kernel machine regression (BKMR), and restricted cubic splines (RCS) were applied to assess single and mixed metal effects on CKD risk, while network toxicology and mediation/moderated mediation analyses were used to explore mechanisms and lifestyle interactions. Higher serum Li, Ni, and Mn concentrations and LNCM mixture exposure were positively associated with CKD risk, with Li contributing most strongly (weight = 0.563). Network toxicology suggested lipid metabolism as a potential pathway, and mediation analysis indicated that triglycerides (TG) mediated 7.76%-11.00% of the metal-CKD associations. Healthy lifestyle behaviors attenuated TG elevation induced by LNCM exposure. These findings suggested that mixed exposure to Li, Ni, Co, and Mn were associated with increased CKD risk in older adults, with TG partially accounting for these associations, and that healthy lifestyle behaviors might attenuate these observed relationships.