Uranium nephrotoxicity

Because the drug and the mobilized metals are excreted via the urine, the drug is contraindicated in anuric patients. Nephrotoxicity from EDTA has been reported, but in most cases this can be prevented by maintenance of adequate urine flow, avoidance of excessive doses, and limitation of a treatment course to 5 or fewer consecutive days. EDTA may result in temporary zinc depletion that is of uncertain clinical significance. An experimental analog of EDTA, calcium disodium diethylenetriaminepentaacetic acid (DTPA), has been used for removal ("decorporation") of uranium, plutonium, and other heavy radioisotopes from the body. 

Tolson, J.K., Roberts, S.M., Jortner, B., Pomeroy, M., Barber, D.S. (2005). Heat shock proteins and acquired resistance to uranium nephrotoxicity. Toxicology 206 59-73. 

Domingo JL, de la Torre A, Belles M, et al. 1997. Comparative effects of the chelators sodium 4,5-dihydroxybenzene-l,3-disulfonate (tiron) and diethylenetriaminepentaacetic acid (dtpa) on acute uranium nephrotoxicity in rats. Toxicology 118( 1 ) 49-59. 

Melgard R. 1980. In Kathren RL, Weber JR, eds. Ultrasensitive techniques for measurement of uranium in biological samples and the nephrotoxicity of uranium, Washington, DC, Dec. 4-5, 1985. Richland, WA Pacific Northwest Laboratory, 1-9. 

For treatment when acute nephrotoxicity is possible, alkalinization of the urine is important to increase urinary excretion of uranium. Systemic chelating agents, such as calcium or zinc salts of diethylenetria-minepentaacetic acid (Ca-DTPA or Zn-DTPA), although recommended in some publications, have not been shown to be useful in increasing the excretion of uranium. 

B. To produce urinary aikaiinization, to enhance elimination of certain acidic drugs (salicylate, phenobarbital, chlorpropamide, chiorophenoxy herbicides-2,4-D), and to prevent nephrotoxicity from the renal deposition of myoglobin after severe rhabdomyoiysis or precipitation of methotrexate. (While enhanced elimination may be achieved, it is uncertain if clinical outcomes are improved with this therapy.) Also recommended by REAC/TS for internal contamination of uranium from radiation emergencies to prevent acute tubular necrosis (see Radiation, p 327). 

Selden, A.L., Lundhohn, C., Edlund, B. et al. (2009). Nephrotoxicity of uranium in drinking water from private drilled wells. Environ. Res. 109, 486-494. 

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