Urinary zinc-lead and strontium-iron combinations affect renal function via serum uric acid: A cross-sectional study...

The relationships between urinary metal mixture exposures and CKD, as well as the mediating role of serum uric acid (SUA), remain unexplored. The study analyzed baseline data from the China Multi-Ethnic Cohort (CMEC) of 14,806 adults. Urinary concentrations of 21 metals were quantified using inductively coupled plasma mass spectrometry. Least absolute shrinkage and selection operator (LASSO) regression was used to identify key metals, and their associations with CKD were assessed using logistic regression and restricted cubic splines. To comprehensively assess all possible combinations of the selected metals, Mixture effects were analyzed through Qgcomp and WQS regression. Significant metal combinations and their interactions were further assessed, while the mediating role of SUA was evaluated using generalized linear models. Multiple sensitivity analyses were used to ensure robustness. LASSO regression identified six primary urinary metals (Zn, Sr, Mo, Pb, B, and Fe) from a total of 21 metals analyzed. In the single-metal models, Sr and Fe exhibited inverse associations with CKD, though causality requires further investigation given potential confounding by altered renal excretion. Conversely, Zn indicated a significant positive association with CKD. In mixture analyses, the qgcomp revealed significant heterogeneity across all 63 combinations, and the directional consistency with single-metal models was maintained. WQS confirmed stability in the weight directions. Among 63 metal combinations. Zn + Pb exhibited risk-enhancing effects through a synergistic interaction, while Sr + Fe demonstrated the strongest inverse association without significant multiplicative interaction. Uric acid mediated 24.9 % and 22.7 % of the Sr + Fe-CKD and Zn + Pb-CKD effects, respectively. This study highlights the individual or combined effects of six urinary metals (Zn, Sr, Mo, Pb, B, and Fe) on CKD, focusing on the specific urinary metal combinations (Zn + Pb and Sr + Fe) mediated by SUA, providing novel insights into the associations of metal with CKD.