Associations of Prenatal Metals Exposure with Kidney Injury Biomarkers in Children

Background and Aim: Prenatal exposure to toxic metal(loid)s, including arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) during development may have nephrotoxic effects in children. We assessed associations between prenatal metal exposure and urinary kidney injury biomarkers in children. Methods: Analyses included 418 children participating in the PROGRESS birth cohort study in Mexico City. Concentrations of As, Cd, Pb, and Hg (urine only) were quantified in maternal second trimester (2T) blood and urine. Kidney parameters were assessed at 8-10 years of age. We examined associations between individual metals and 1) kidney injury biomarkers using linear regression and 2) a multi-protein kidney index using weighted quantile sum (WQS) regression. Associations of separate urine and blood metal mixtures with individual kidney injury biomarkers were assessed via WQS. Covariates included child’s age, sex, body mass index z-score, urine creatinine, 2T socioeconomic status, and 2T smoking exposure. Results: In single metal analyses, doubling of urine Cd was associated with higher urinary TIMP metallopeptidase inhibitor 1 (TIMP1), alpha-1-microglobulin (A1M), clusterin, and cystatin C. Within the multi-protein index, the association with increased urinary As was predominated by albumin, fatty acid binding protein 1 (FABP1), and interferon gamma-induced protein 10 (IP10), and the association with increased urinary Cd was predominated by albumin, A1M, TIMP1, lipocalin, and FABP1. Decile increases in urine metal mixture was associated with increased urinary albumin, IP10, and cystatin C. Urinary As and Cd comprised 60-96% of the metal mixture weights contributing to the associations. Conclusions: Prenatal urinary metals, individually and as a mixture were associated with increased urinary kidney injury biomarkers in healthy children. Prenatal metals exposure may lead to subclinical glomerular or tubular injury in school age children. Further research is required to ascertain resolution or worsening of subclinical kidney injury at later life stages. Keywords: Heavy metals; Renal health; Mixtures