Nephrotoxic and Non-Nephrotoxic Metal Mixtures and Kidney Function in Early Pregnancy – a Cross-Sectional Analysis in Project Viva

Some metals are established nephrotoxicants, yet their associations with kidney function remain understudied in the context of pregnancy, a time of substantial change in kidney physiology and function. We aimed to estimate the individual and joint associations of metal mixtures with maternal kidney function during the 1st trimester of pregnancy (mean 9.7 gestational weeks). 1040 women from Project Viva contributed blood samples which were assessed for erythrocyte nephrotoxic [arsenic (As), cadmium (Cd), cesium (Cs), mercury (Hg), lead (Pb)] and non-nephrotoxic [barium (Ba), magnesium (Mg), manganese (Mn), selenium (Se), and Zinc (Zn)] metals, and plasma creatinine for kidney function. We estimated glomerular filtration rate using the Chronic Kidney Disease Epidemiology Collaboration (eGFRCKD-EPI) equation without race-adjustment factors. We examined associations of eGFRCKD-EPI with individual metals using multivariable linear regression and their mixtures using quantile-based g-computation, adjusting for sociodemographics, pregnancy characteristics, and diet. Participants in our study were predominantly of white/non-Hispanic race/ethnicity (75%), college graduates (72%), and had household income >$70,000/year (63%). After adjusting for covariates, higher Pb (β -3.51 ml/min/1.73 m; 95% CI -5.83, -1.18) concentrations were associated with lower eGFRCKD-EPI, while higher Mg (β 10.53 ml/min/1.73 m; 95% CI 5.35, 15.71), Se (β 5.56 ml/min/1.73 m; 95% CI 0.82, 10.31), and Zn (β 5.88 ml/min/1.73 m; 95% CI 0.51, 11.26) concentrations were associated with higher eGFRCKD-EPI. In mixture analyses, higher nephrotoxic metal mixture concentration was associated with reduced eGFRCKD-EPI (Ψ -1.03 ml/min/1.73 m; 95% CI: -1.92, -0.14). Conversely, higher non-nephrotoxic metal mixture concentration was associated with higher eGFR (Ψ 1.42; 95% CI: 0.48, 2.37). Exposure to metals in early pregnancy may influence women’s kidney function although reverse causation cannot be eliminated in this cross-sectional analysis. These findings have important implications for long-term cardiovascular and postpartum kidney health that warrant additional studies.