Kidneys uranium toxicity

The mechanism for the renal toxicity observed in cases of adult exposure to uranium is believed to be due to the retention of uranium in the kidney. This is the result of the reabsorption of bicarbonate from the ultrafiltrate in the proximal tubule and the resulting release of the U02 ion from a bicarbonate complex. Newborn humans have relahvely inefficient tubular secretion and reabsorption compared to older children or adults, and whether this would increase or decrease the susceptibility of newborns to uranium toxicity is not known. 

Methods for Reducing Toxic Effects. Uranium forms complexes with the bicarbonate ion (Cooper et al. 1982) and has been administered prophylactically after uranium exposure (Fisher et al. 1991). Bicarbonate can alkalize the blood to a degree that facilitates the excretion of uranium via the kidneys. This in turn, can prevent uptake by and deposition in critical tissues (kidney, bone). Chelation has been tested in animals and found to have a limited potential, though possibly valuable, role in reducing acute uranium toxicity. Further research is needed to validate, refute, or refine method(s) for reducing the toxic effects of uranium compounds. No verified methods for reducing the toxic effects of long-term exposure to uranium are currently available. 

A study by the oral route establishing a threshold for renal effects in weanling and adult rats of the same strain is needed to determine if susceptibility to uranium toxicity varies with age. Histopathological studies and urinalysis should be performed, as well as measurement of uranium in excreta for both groups. At termination in this study, uranium content should be measured in tissues, particularly bone and kidney. This will provide information on whether retention of uranium in bone is age-dependent (as assumed by analogy with calcium in PBPK models) and on whether kidney burden associated with uranium toxicity is age-related. 

An interesting review (Arzuaga et al. 2010) of the kidney toxicity effects of longterm exposure to natural uranium and DU states that The kidney was observed to be a target of uranium toxicity following oral and implantation exposure routes in several animal species. The interpretation and importance of the observed changes in biomarkers of proximal tubule function are important questions that indicate the need for additional clinical, epidemiological, and experimental research. ... 

Uranium as of 12/08/03 zero as of 12/08/03 30ug/L Increased risk of cancer, kidney toxicity Erosion of natural deposits... 

Animal studies indicate that the primary toxic effect of uranium exposure is on the kidney, with particular damage to the proximal tubules. Functionally, this may result in increased excretion of glucose and amino acids. Structurally the necrosis of tubular epithelium leads to formation of cellular casts in the urine. If exposure is insufficient to cause death from renal failure, the mbular lesion is reversible with epithelial regeneration. Although bone is the other major site of deposition, there is no evidence of toxic or radiocarcinogenic effects to bone or bone marrow from experimental studies. ... 

Thiebault, C., Carriere, M., Milgram, S., Simon, A., Avoscan, L., Gouget, B. (2007). Uranium induces apoptosis and is geno-toxic to normal rat kidney (NRK-52E) proximal cells. Toxicol. Set 98 479-87. 

Urinary excretion data were used in a kinetic model to estimate the maximum uranium kidney concentrations of workers accidentally exposed to uranium hexafluoride (Fisher et al. 1990). Initial intakes of workers involved in the accident ranged from 470 to 24,000 pg uranium. The model estimated the maximum kidney concentrations in the workers as ranging from 0.048 to 2.5 pg U/g in kidney tissue renal toxicity was not observed in any of the workers (Fisher et al. 1990). 

The dual modes of uranium chemical and radiological toxicity are not usually separately identifiable by end point. The renal and respiratory effects from exposure of humans and animals to uranium are usually attributed to the chemical properties of uranium, while the theoretically potential excess cancers are usually attributed to the radiation properties of this substance. Although the net effects on the lungs and kidneys have been suggested to be a cooperative action of the chemical and radiation properties, with a complementary mechanism of action, this relationship has not been demonstrated experimentally (Ballou... 

The chemical action of all isotopes and isotopic mixtures of uranium are identical, regardless of the specific activity, because chemical action depends only on chemical properties. Thus, the chemical toxicities of natural, depleted, and enriched uranium are identical. Current evidence from animals studies suggests that the toxicity of uranium is mainly due to its chemical damage to kidney tubular cells, leading to nephritis. 

Animal studies designed to examine the combined effects on the kidney of uranium and other heavy metal nephrotoxicants Gead, cadmium) would also be useful to determine whether effects are less than expected on the basis of individual toxicity, additive or synergistic. It is possible at some waste sites that multiple exposures to these metals could occur in humans. 

Stopps GJ, Todd M. 1982. The chemical toxicity of uranium with special reference to effects on the kidney and the use of urine for biological monitoring. Prepared for the Atomic Energy Control Board, Ottawa, Canada. CA 8306480. NTIS DE 84-701123. 

In contrast, the chemical toxicity of uranium is more important than its radiological hazard. In body fluids, uranium is present as soluble U(VI) species and is rapidly eliminated from the body (60% within 24 h Goyer and Clarkson (2001)). It is rapidly absorbed from the gastrointestinal tract and moves quickly through the body. The uranyl carbonate complex in plasma is filtered out by the kidney glomerulus, the bicarbonate is reabsorbed by the proximule tubules, and the liberated uranyl ion is concentrated in the tubular cells. This produces systemic toxicity in the form of acute renal damage and renal failure. 

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