The accurate assessment of risk associated with exposures to nephrotoxic metals demands an explicit understanding of relationships between level of exposure, the resulting dose to the kidney and effects on kidney function. Development of methods for directly measuring or predicting kidney burden of metals in humans is a central component of this problem. Experiments in laboratory animals allow a rigorous exploration of the biokinetics of metals in kidney and can lead to development of models relating level of exposure to kidney metal burden, and the latter to other biological indices of kidney burden (e.g. Urinary metal) and nephrotoxicity (e.g, proteinuria). However, extrapolation of these models to humans can not be made with certainty, unless they can be validated with quantitative assessments in humans. Methods for in vivo measurement or estimation of metals in kidney can be used to test models that are based on laboratory animal data, and thus, potentially, can lead to a greatly improved understanding of exposure-effect relationships for nephrotoxic metals in humans.
KeywordsIsotope Dilution Inorganic Mercury Outer Medulla Renal Uptake Isotope Dilution Method
Unable to display preview. Download preview PDF.
- 4.K.J. Ellis and S.P. Kelleher, In vivo bone aluminum measurement in patients with renal disease, In: “In Vivo Body Composition Studies,” K.J. Ellis, S. Yasamura, and W.D. Morgan, eds., Institute of Physical Science and Medicine, London (1987).Google Scholar
- 11.A. Rothstein and A.D. Hayes, The metabolism of mercury in the rat studied by isotope techniques, J. Pharmacol. Exp. Ther. 130: 166–176 (1960).Google Scholar
- 13.J.B. Hursh, M.R. Greenwood, T.W. Clarkson, J. Allen and S. Demuth, The effect of ethanol on the fate of mercury inhaled by man, J. Pharmacol. Exp. Ther. 214: 420–427 (1980).Google Scholar
- 16.H. Satoh, J.B. Hursh and T.W. Clarkson, Selective determinations of elemental mercury in blood and urine exposed to mercury vapor in vitro, Appl. Toxicol. 1: 177–181 (1968).Google Scholar
- 21.M. Berlin, Dose-response relationships and diagnostic indices of mercury and mercurials, In: Effects and Dose-Response Relationships of Toxic Metals, G.G. Nordberg, ed., Elsevier Scientific Publishing Co., Amsterdam (1976).Google Scholar
- 25.T.W. Clarkson, L. Magos, C. Cox, M.R. Greenwood, L. Amin-Zaki, M.A. Majeed and S.F. Al-Damluji, Tests of efficacy of antidotes for removal of methylmercury in human poisoning during the Iraqui outbreak, J. Pharmacol. Exp. There 218:74–83 (1981).Google Scholar
- 26.J.J. Chisolm and D.J. Thomas, Use of 2,3-dimercaptopropane-1-sulfonate in treatment of lead poisoning in children, J. Pharmacol. Exp. Ther. 235: 605–624 (1985).Google Scholar