Occupational and environmental exposures to toxic metals are established risk factors
for the development of hypertension and kidney disease in adults. There is some evidence
of developmental metal nephrotoxicity in children and from animal studies; however,
to our knowledge no previous studies have examined associations between co-exposure
to nephrotoxic environmental metals and children’s kidney health. The objective of
this study was to assess the association between co-exposure to lead (Pb), cadmium
(Cd), mercury (Hg), and arsenic (As), measured in urine and blood, and kidney parameters
in US adolescents. We performed a cross-sectional analysis of a subsample of 2,709
children aged 12–19 participating in the National Health and Nutrition Examination
Survey (NHANES) between 2009 and 2014. We analyzed urine levels of 4 nephrotoxic metals
selected a priori (As, Cd, Pb and Hg), U mix , and 3 nephrotoxic metals in blood (Cd,
Pb, and Hg), B mix , using a weighted quantile sum (WQS) approach. We applied WQS
regression to analyze the association of B mix and U mix with estimated glomerular
filtration rate (eGFR), serum uric acid (SUA), urine albumin, blood urea nitrogen
(BUN), and systolic blood pressure (SBP), adjusting for sex, race/ethnicity, age,
head of household’s education level, height, BMI, serum cotinine, and NHANES cohort
year. U mix and urine albumin models were also adjusted for urine creatinine, and
B mix models were also adjusted for fish consumption. Subanalyses included stratification
by sex and an arsenic-only model including six speciated forms of As measured in urine.
In WQS regression models, each decile increase of U mix was associated with 1.6%
(95%CI: 0.5, 2.8) higher BUN, 1.4% (95%CI: 0.7, 2.0) higher eGFR, and 7.6% (95%CI:
2.4, 13.1) higher urine albumin. The association between U mix and BUN was primarily
driven by As (72%), while the association with eGFR was driven by Hg (61%), and Cd
(17%), and the association with urine albumin was driven by Cd (37%), Hg (33%), and
Pb (25%).There was no significant relationship between U mix and SUA or SBP. In WQS
models using the combined blood metals, B mix , each decile increase of B mix was
associated with 0.6% (95%CI: 0.0, 1.3) higher SUA; this association was driven by
Pb (43%), Hg (33%), and Cd (24%) and was marginally significant (p=0.05). No associations
were observed between B mix and urine albumin, eGFR, BUN, or SBP. The findings suggest
metals including As, Pb, Hg, Cd and their combinations may affect renal parameters,
although potential reverse causation cannot be ruled out due to the cross-sectional
study design. Implications of early life low-level exposure to multiple metals on
kidney function may have far-reaching consequences later in life in the development
of hypertension, kidney disease, and renal dysfunction. Longitudinal studies should
further evaluate these relationships.