Prenatal Metal Exposures and Associations with Kidney Injury Biomarkers in Children

Abstract

Prenatal exposure to arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) may be nephrotoxic, yet limited studies have examined subclinical kidney injury biomarkers in children. We assessed whether metal exposure in the second trimester (2T), a crucial time of kidney development, is associated with altered urine kidney injury and function biomarkers in preadolescent children. Analyses included 494 children participating in a birth cohort study in Mexico City. Concentrations of As, Cd, and Pb were measured from pregnant women in 2T blood and urine, and Hg in urine only. Kidney biomarkers were measured from children in urine at age 8–12 years. We assessed the associations between individual metals and (1) kidney biomarkers using linear regression and (2) a multi-protein kidney mixture using weighted quantile sum (WQS) regression. Associations of separate urine and blood metal mixtures with individual kidney biomarkers were assessed via WQS. Within the multi-protein mixture, the association with increased urinary As was predominated by urine alpha-1-microglobulin (A1M), interferon gamma-induced protein 10 (IP10), and fatty acid binding protein 1; the association with increased urinary Cd was predominated by A1M, clusterin, and albumin. The urine metal mixture was associated with increased albumin (0.23 ng/mL; 95% confidence interval (CI): 0.10, 0.37), IP10 (0.15 ng/mL; 95% CI: 0.02, 0.28), and cystatin C (0.17 ng/mL; 95% CI: 0.04, 0.31); these associations were mainly driven by urinary As and Cd. We observed null associations between prenatal blood or urine metal mixtures and estimated glomerular filtration rate. Higher prenatal urinary metals, individually and as a mixture were associated with altered kidney injury biomarkers in children. Further research and longer participant follow-up are required to ascertain the risk of kidney disease later in life.

Multimetal exposure: Challenges in diagnostics, prevention, and treatment

“…Pronephros developmental frame is equivalent to about gestation period of 3-4 weeks in the human fetus. [86] In an epidemiological study, Politis et al [87] reported that prenatal metals exposure was related to kidney damage biomarkers in the urine of healthy children. Metal exposure during pregnancy may cause damage in the glomeruli or tubules in the offspring, which can impact the susceptibility to kidney damage in the later stages of life.…”

“…Metal exposure during pregnancy may cause damage in the glomeruli or tubules in the offspring, which can impact the susceptibility to kidney damage in the later stages of life. [ 87 ] Jain reported synergistic effects of combined exposure to Pb, Cd, and Hg on the nephrotoxicity in a cross‐sectional study. For instance, when people were exposed to high amounts of two metals (Pb and Cd), their adjusted odds ratios (AORs) for unhealthy kidney function were more as compared to when they were exposed to only one metal (e.g., Pb).…”

Metabolism-Disrupting Chemical Mixtures during Pregnancy, Folic Acid Supplementation, and Liver Injury in Mother-Child Pairs

“…MDC estimates (outdoor air pollutants) and biomarkers (metals/metalloids, pesticides, phthalates) in pregnant women were measured as previously detailed. [26][27][28][29] Briefly, we estimated daily concentrations in the Mexico City Metropolitan Area at 1-km 2 grids for two air pollutants (PM2.5, NO2) based on household location using validated spatiotemporal models and satellite information. [28,30] We then averaged concentrations for the three pregnancy trimesters.…”

A Cross-Sectional Analysis Investigating Pregnant Women’s Renal Function and Its Association with Lead and Cadmium Exposures—The DSAN Birth Cohort Study in Recôncavo Baiano, Brazil

“…Should the kidneys not maintain the necessary changes, such as an increase in eGFR, spontaneous abortion has been recorded [ 1 ]. Furthermore, studies have described associations with preeclampsia in pregnant people with lead and cadmium exposures [ 12 , 13 ] and the development of kidney disease in the general population and in children with prenatal non-essential metal exposures [ 14 , 15 ]. Few studies have focused on the deleterious outcomes of toxic metals on the pregnant person’s kidney health instead of pregnancy outcomes [ 16 , 17 , 18 ].…”