TY - JOUR
T1 - Nephrotoxic metal mixtures and preadolescent kidney function
AU - Levin-Schwartz, Yuri
AU - Politis, Maria D.
AU - Gennings, Chris
AU - Tamayo-Ortiz, Marcela
AU - Flores, Daniel
AU - Amarasiriwardena, Chitra
AU - Pantic, Ivan
AU - Tolentino, Mari Cruz
AU - Estrada-Gutierrez, Guadalupe
AU - Lamadrid-Figueroa, Hector
AU - Tellez-Rojo, Martha M.
AU - Baccarelli, Andrea A.
AU - Wright, Robert O.
AU - Sanders, Alison P.
N1 - Publisher Copyright:
© 2021 by the authors.
PY - 2021/8
Y1 - 2021/8
N2 - Exposure to metals including lead (Pb), cadmium (Cd), and arsenic (As), may impair kidney function as individual toxicants or in mixtures. However, no single medium is ideal to study multiple metals simultaneously. We hypothesized that multi-media biomarkers (MMBs), integrated indices combining information across biomarkers, are informative of adverse kidney function. Levels of Pb, Cd, and As were quantified in blood and urine in 4-6-year-old Mexican children (n = 300) in the PROGRESS longitudinal cohort study. We estimated the mixture effects of these metals, using weighted quantile sum regression (WQS) applied to urine biomarkers (Umix), blood biomarkers (Bmix), and MMBs, on the cystatin C-based estimated glomerular filtration rate (eGFR) and serum cystatin C assessed at 8-10 years of age, adjusted for covariates. Quartile increases in Umix and the MMB mixture were associated with 2.5% (95%CI: 0.1, 5.0) and 3.0% (95%CI: 0.2, 5.7) increased eGFR and -2.6% (95% CI: -5.1%, -0.1%) and -3.3% (95% CI: -6.5%, -0.1%) decreased cystatin C, respectively. Weights indicate that the strongest contributors to the associations with eGFR and serum cystatin C were Cd and Pb, respectively. MMBs detected mixture effects distinct from associations with individual metals or media-type, highlighting the benefits of incorporating information from multiple exposure media in mixtures analyses.
AB - Exposure to metals including lead (Pb), cadmium (Cd), and arsenic (As), may impair kidney function as individual toxicants or in mixtures. However, no single medium is ideal to study multiple metals simultaneously. We hypothesized that multi-media biomarkers (MMBs), integrated indices combining information across biomarkers, are informative of adverse kidney function. Levels of Pb, Cd, and As were quantified in blood and urine in 4-6-year-old Mexican children (n = 300) in the PROGRESS longitudinal cohort study. We estimated the mixture effects of these metals, using weighted quantile sum regression (WQS) applied to urine biomarkers (Umix), blood biomarkers (Bmix), and MMBs, on the cystatin C-based estimated glomerular filtration rate (eGFR) and serum cystatin C assessed at 8-10 years of age, adjusted for covariates. Quartile increases in Umix and the MMB mixture were associated with 2.5% (95%CI: 0.1, 5.0) and 3.0% (95%CI: 0.2, 5.7) increased eGFR and -2.6% (95% CI: -5.1%, -0.1%) and -3.3% (95% CI: -6.5%, -0.1%) decreased cystatin C, respectively. Weights indicate that the strongest contributors to the associations with eGFR and serum cystatin C were Cd and Pb, respectively. MMBs detected mixture effects distinct from associations with individual metals or media-type, highlighting the benefits of incorporating information from multiple exposure media in mixtures analyses.
KW - Arsenic
KW - Cadmium
KW - Childhood
KW - Kidney
KW - Lead
KW - Mixture
UR - http://www.scopus.com/inward/record.url?scp=85112745261&partnerID=8YFLogxK
U2 - 10.3390/children8080673
DO - 10.3390/children8080673
M3 - Article
AN - SCOPUS:85112745261
SN - 2227-9067
VL - 8
JO - Children
JF - Children
IS - 8
M1 - 673
ER -