Isotopic Fractionation of Natural Uranium in Mice as a Potential Biomarker of Renal Accumulation

Chronic low-level uranium (U) exposure through drinking
water is
a public health risk in the United States. Nearly two-thirds of community
water systems, serving 320 million people, have detectable U levels,
with 2% exceeding the EPA’s maximum contaminant level of 30
μg/L. Ingested U accumulates in kidneys and is nephrotoxic at
high levels. Uranium binds to proximal tubule cells, causing injury
and interfering with kidney function. Epidemiological studies suggest
that even low-level (<30 μg/L) of U exposure could damage
kidneys. Current biomarkers, like urinary U levels, fail to indicate
tissue-specific concentrations and metabolic interactions in kidneys.
Fractionation of 238U/235U may potentially serve
as a biomarker for the metabolic interaction of U with organs. Our
experiments with mice showed changes in U isotopic composition (238U/235U expressed as δ238U) in
organs after administering 50 mg/L U via drinking water for 2, 7,
and 14 days. We found 235U enrichment in kidneys and bones,
the target organs, while urine was enriched in 238U. Our
results provide evidence of isotopic fractionation resulting from
U accumulation in kidneys. Urinary U isotopic composition may, thus,
provide a sensitive, noninvasive measurement of renal U bioaccumulation
that could aid early detection of nephrotoxicity and prevention of
irreversible kidney damage.