Critical windows of prenatal and early life exposure to toxic metals and early childhood kidney function

Abstract

Introduction: As renal development and maturation processes begin in utero and continue through early childhood, metal exposures during these periods may be sensitive windows for subclinical renal toxicity in children with implications for later life risk of hypertension and kidney disease. We used novel dentine biomarkers of toxic metal exposure to identify critical windows of susceptibility to lead (Pb) and chromium (Cr) and associations with children’s kidney function at age 8-9 years.Methods: Participants included 86 children in the Programming Research in Obesity Growth, Environment and Social Stress (PROGRESS) longitudinal birth cohort study based in Mexico City. Estimated glomerular filtration rate (eGFR) was assessed for children 8-9 years of age using serum cystatin C measures, while pre- and postnatal Pb and Cr concentrations were reconstructed in weekly increments by analyzing deciduous teeth with laser ablation-inductively coupled plasma-mass spectrometry. We used reverse distributed lag models (rDLMs) to examine time-varying associations between weekly metal exposure and children’s eGFR while adjusting for child’s age, sex, and height.Results: We identified a critical window of susceptibility to Pb exposure, wherein postnatal Pb exposure 24-26 weeks after birth was associated with children’s decreased eGFR at 8 to 9 years of age. We also identified both pre- and postnatal windows of vulnerability to Cr exposure associated with decreased eGFR in children.Conclusions: Using tooth-matrix biomarkers, we identified discrete developmental exposure windows wherein Pb and Cr were associated with reduced renal function in childhood. Further work investigating eGFR trajectories with longitudinal measures through adolescence will be important to understanding the implications of these findings for later life renal health.