Uranium exposure and kidney tubule biomarkers in the Multi-Ethnic Study of Atherosclerosis (MESA).
Background: Experimental studies indicate that uranium exposure is toxic to the kidney tubules. We evaluated the association of urinary uranium concentrations with biomarkers of tubule cell dysfunction (alpha-1-microglobulin [A1M], uromodulin [UMOD], epidermal growth factor [EGF]), and tubule cell injury (kidney injury molecule-1 [KIM-1], monocyte chemoattractant protein-1 [MCP-1], and chitinase-3-like protein 1 [YKL-40]), as well as with albuminuria and estimated glomerular filtration rate (eGFR) among participants in the Multi-Ethnic Study of Atherosclerosis (MESA).
Methods: We conducted a cross-sectional study that included 461 participants selected for the absence of diabetes, chronic kidney disease (CKD), and cardiovascular disease, evaluated with six kidney tubule biomarker measurements. Urinary uranium concentrations were measured using inductively coupled plasma mass spectrometry in spot urine samples. Linear models were used to determine associations of urinary uranium concentrations with each kidney tubule biomarker, calculated by the geometric mean ratio (GMR), after adjustment for participant's urinary creatinine concentrations, age, sex, race/ethnicity, MESA field center, highest level of education completed, cigarette smoking status, alcohol consumption, body mass index (BMI), albuminuria levels, and eGFR.
Results: Median (interquartile range) urinary uranium concentration was 5.2 (2.9, 10.4) ng/L, and mean (standard deviation) eGFR was 99 (16) mL/min/1.73 m2. The adjusted GMRs (95%CI) of KIM-1 and MCP-1 were 1.11 (1.01, 1.22) and 1.10 (1.01, 1.20), respectively per 7.5 ng/L (interquartile range) higher urinary uranium concentration, while no statistically significant associations were observed for YKL-40, A1M, UMOD, EGF, albuminuria, or eGFR. In flexible dose-response models, the associations were positive and largely linear between urinary uranium concentrations and higher KIM-1 and MCP-1.
Conclusions: Among healthy community-living individuals, chronic low-level uranium exposure, as measured in urine, was associated with markers of kidney tubule cell injury. Chronic low-level uranium exposure observed in contemporary US urban centers may adversely affect kidney tubule health and related outcomes.