Anderson WA, Domingo-Relloso A, Galvez-Fernandez M, Schilling K, Glabonjat RA, Basu A, Nigra AE, Gutierrez OM, Scherzer R, Goldsmith J, Sarnak MJ, Bonventre JV, Kimmel PL, Vasan RS, Ix JH, Shlipak MG, and Navas-Acien A
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 m 2 . 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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Orlando M. Gutierrez reports financial support was provided by Amgen Inc. Orlando M. Gutierrez reports financial support was provided by AstraZeneca Pharmaceuticals LP. Orlando M. Gutierrez reports financial support was provided by Ardelyx Inc. Joseph V. Bonventre reports a relationship with Sarepta Therapeutics Inc that includes: consulting or advisory. Joseph V. Bonventre reports a relationship with PRAXIS that includes: consulting or advisory. Joseph V. Bonventre reports a relationship with Nimbus Therapeutics Inc that includes: consulting or advisory. Joseph V. Bonventre reports a relationship with GentiBio that includes: consulting or advisory. Joseph V. Bonventre reports a relationship with Innoviva Inc that includes: equity or stocks. Joseph V. Bonventre reports a relationship with MediBeacon that includes: equity or stocks. Joseph V. Bonventre reports a relationship with DxNow that includes: equity or stocks. Joseph V. Bonventre reports a relationship with Verinano that includes: equity or stocks. Joseph V. Bonventre reports a relationship with Autonomous Medical Devices, Inc. that includes: equity or stocks. Joseph V. Bonventre reports a relationship with Renalytix AI Inc that includes: equity or stocks. Joseph V. Bonventre has patent #10712349 issued to Brigham & Women's Hospital. co-author is an editorial board member of Environmental Research - Ana Navas-Acien. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Inc. All rights reserved.)