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

29 Pages Posted: 19 May 2022

See all articles by Pi-I Debby Lin

Pi-I Debby Lin

Harvard University - Harvard Medical School

Andres Cardenas

affiliation not provided to SSRN

Sheryl Rifas-Shiman

affiliation not provided to SSRN

Ami Zota

affiliation not provided to SSRN

Marie-France Hivert

affiliation not provided to SSRN

Izzuddin M. Aris

Harvard University - Harvard Medical School

Alison Sanders

University of Pittsburgh

Abstract

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 m2; 95% CI -5.83, -1.18) concentrations were associated with lower eGFRCKD-EPI, while higher Mg (β 10.53 ml/min/1.73 m2; 95% CI 5.35, 15.71), Se (β 5.56 ml/min/1.73 m2; 95% CI 0.82, 10.31), and Zn (β 5.88 ml/min/1.73 m2; 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 m2; 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.

Keywords: Metals, pregnancy, eGFR, kidney function

Suggested Citation

Lin, Pi-I Debby and Cardenas, Andres and Rifas-Shiman, Sheryl and Zota, Ami and Hivert, Marie-France and Aris, Izzuddin M. and Sanders, Alison, Nephrotoxic and Non-Nephrotoxic Metal Mixtures and Kidney Function in Early Pregnancy – a Cross-Sectional Analysis in Project Viva. Available at SSRN: https://ssrn.com/abstract=4114266 or http://dx.doi.org/10.2139/ssrn.4114266

Pi-I Debby Lin

Harvard University - Harvard Medical School

Andres Cardenas

affiliation not provided to SSRN ( email )

Sheryl Rifas-Shiman

affiliation not provided to SSRN ( email )

Ami Zota

affiliation not provided to SSRN ( email )

Marie-France Hivert

affiliation not provided to SSRN ( email )

Izzuddin M. Aris (Contact Author)

Harvard University - Harvard Medical School ( email )

25 Shattuck St
Boston, MA 02115
United States

Alison Sanders

University of Pittsburgh ( email )

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