Experimental Study of Acquired Resistance of the Rabbit's Renal Epithelium to Uranyl Nitrate

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Abstract
Although the ability of renal epithelium to regenerate after injury has been frequently demonstrated, little is known concerning the nature of the new cells. The purpose of this study was to determine whether regenerated kidney cells are as susceptible to injury by nephrotoxins as the original epithelium or become resistant or immune to such substances. The experimental work of Gil y Gil, the only previous investigator, has been repeated and confirmed. Preliminary experiments showed that 0.001 gm. of uranium subcutaneously or 0.0005 gm. intravenously, each representing f the lethal dose for rabbits, regularly kills normal proximal convoluted tubular epithelium. Complete regeneration occurs in 2 weeks. Differences in morphology and staining readily distinguish the new epithelium from the original. Ample time for regeneration was allowed between the periodically increased injections. Only those animals surviving the last injection sufficiently long for fresh necrosis to appear in the persisting original tubular cells and less than the time required for new regeneration to begin are included in the series. A high degree of acquired resistance to uranium is evidenced by lack of microscopic changes in the regenerated epithelium after giving 54-96 times the amount known to kill the original cells in the same tubules. Intravital staining indicated that the regenerated tubules were patent. Qualitative chemical tests and biological experiments proved that chronic uranium kidneys were able to excrete the metal in greater quantities than acutely damaged organs. The acquired resistance may be due either to the cells detoxicating the poison or to preventing its combination with their proteins. In rabbits long-continued repeated administration of uranium leads to marked chronic glomerulo-tubular lesions with secondary contraction.

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