Review of the Toxicologic and Radiologic Risks to Military Personnel from Exposures to Depleted Uranium During and After Combat (2008) / Chapter Skim
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3 Toxic Effects of Uranium on the Kidneys
3 Toxic Effects of Uranium on the Kidneys
Pages 26-42
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From page 26... ...
BACKGROUND Acute uranium exposure produces degeneration of renal tubular epithelium followed by regeneration. Biomarkers or biochemical indicators of effects of uranium exposure on various aspects of renal function are available, and those cited in animal and human studies are listed in Table 3-1.
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From page 27... ...
Uranium exposure may also produce glomerular injury that results in leakage of albumin and other highmolecular-weight proteins. Renal failure is characterized by inability to excrete metabolic wastes and is reflected by increases in nonprotein nitrogen (NPN)
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From page 28... ...
1996 glucosuria persisted beyond 32 wk of observation Skin (burn) Nitrate 1 male 130 35 +++ Peak renal tubular Zhao and Zhao 1990 dysfunction after 7 d; normal after 1 mo Inhalation Tetra-fluoride 1 male 920 10c ++ Renal dysfunction, Zhao and Zhao 1990 including increased NPN and proteinuria and aminoaciduria, 15 mo after exposure but gradual return to normal Injection Nitrate 2 males 16 6 + Increased NPN, urinary Luessenhop et al.
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From page 29... ...
. c Kidney concentration of uranium peaked 60 d after exposure at 10 µg/g, whereas urinary concentration of uranium and indicators of renal dysfunction peaked about 2 mo after exposure.
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From page 30... ...
The peak renal concentration of uranium was estimated to be 10 µg/g 60 d after exposure, and the urinary uranium and indicators of renal dysfunction peaked at about the same time. The Capstone Report indicated that those events occurred much later than predicted by the International Commission on Radiological Protection (ICRP)
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From page 31... ...
described four subjects exposed to uranium-ore dust and six others exposed to uranium hexafluoride. Table 3-2 includes data on one person who had a uranium intake of 20 mg and peak renal uranium concentration estimated to be 1 µg/g, but biochemical indicators of renal dysfunction were negative in all subjects.
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From page 32... ...
The following are brief reviews of reports of exposure and renal effects after three forms of chronic exposure: inhalation of yellowcake or ore by uranium process workers, ingestion of drinking water by the general population, and chronic exposure of Gulf War veterans due to systemic release of uranium from embedded fragments. Exposure information and renal effects are summarized in Table 3-3.
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From page 33... ...
females, 2-570 µg/d Kurttio et al. 2002 Drinking water: Mean/Median: Not determined Positive correlation of urinary 325 persons; mean daily 0.424/0.078 µg/L uranium exposure with fractional intake, 39 µg (7-224 µg)
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From page 34... ...
2007 Embedded metal fragments, 0.002-44.1 µg/g Not determined No increase in RBP in 2005; inhalation exposure to DU oxides of creatinine battery of tests of glomerular and tubular function showed no evidence of effect a Kidney concentrations from Capstone Report as calculated by Royal Society (2002) with ICRP model.
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From page 35... ...
The Royal Society (2002) calculated the renal uranium concentration to be about 0.1 µg/g from ingestion of uranium at 80 µg/L of drinking water.
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From page 36... ...
Urinary and serum concentrations of calcium, phosphate, glucose, albumin, creatinine, and β2m were measured to evaluate possible renal effects. Uranium concentrations over 300 µg/L in drinking water were associated with increased calcium fractional excretion.
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From page 37... ...
Gulf War Cohort Studies Because early animal studies demonstrated the sensitivity of the kidneys to uranium exposure, special attention was paid to renal-function assessments in a cohort of 74 Gulf War veterans exposed to DU from embedded metal fragments. Results of the first examination, in 1993-1994, showed no evidence of a relationship between urinary uranium excretion and clinical measures of adverse renal function (serum creatinine, calcium, phosphate, and uric acid; and urinary creatinine and β2m)
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From page 38... ...
The lowest observed-adverse-effect-level (LOAEL) was 0.7-1.4 µg/g and peaked when renal uranium concentrations were between 3.4 and 5.6 µg/g, followed by progressive reversal of both morphologic and functional effects, returning to normal about 3 wk after the last injection.
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From page 39... ...
Reversibility of uranyl nitrate-induced renal injury was studied in male New Zealand white rabbits exposed at 24 or 600 mg/L in drinking water for 91 d followed by various recovery periods (Gilman et al.
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From page 40... ...
Biomarkers of renal tubular function were not measured; renal effects were evaluated only through histologic examination. Mechanisms of Uranium Renal Toxicity The mechanisms whereby uranium produces injury to the cells of renal tubules and glomeruli are not fully understood.
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From page 41... ...
reviewed several possible mechanisms of uranium-induced glomerular injury, including evidence that uranium produces structural alterations that decrease the glomerular surface area available for filtration. In vitro studies of isolated glomeruli exposed to uranium bicarbonate suggest that a reduction in glomerular filtration rate may result from glomerular contraction and disorganization of the cytoskeleton (Mirto et al.
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From page 42... ...
have been observed at peak renal uranium concentrations as low as 1 µg/g.
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