2 Journal of the Mitchell Society [May 



kidney is largely vascular. We possess, therefore, in uranium 

 a nephrotoxic substance which, when appropriately adminis- 

 tered, is competent to produce the two main types of nephritis. 

 For this reason uranium was the nephrotoxic substance selected 

 to use in the production of nephritides of different severity, in 

 which one or both elements of the kidney concerned in the for- 

 mation of urine were functionating pathologically. 



By the use of such a substance which produces primarily a 

 vascular, and later a tubular nephritis, it was hoped that by 

 studying the physiological response of the kidney at these 

 stages of its pathological reaction, it might be determined which 

 element of the kidney in a nephritis was most concerned in 

 determining the quantitative output of urine. With this object 

 in view in this study diuretics have been employed which effect 

 both the vascular and the epithelial elements of the kidney. 



In the anatomical study of experimental nephritis which has 

 been previously referred to, the nephrotoxic substances em- 

 ployed were potassium dichromate, sodium arsenate, canthari- 

 din and uranium nitrate. During the course of this investiga- 

 tion it was noted that there existed a fairly clear cut correllation 

 between the degree of epithelial involvement in a given nephritis 

 and the total output of urine; whereas, on the other hand, no 

 such histological correllation could be made, within certain lim- 

 itations, between the severity of the vascular pathology and the 

 output of urine. For example, a nephritic animal with a normal 

 urine flow, or a polyuria, would show a vascular reaction which 

 histologically would be similar to the vascular pathology in an 

 anuric animal. The associated epithelial reaction in such stages 

 of a nephritis differed very widely. In the early nephritides 

 with a normal output of urine, or a polyuria, the ej)ithelial 

 involvement was slight or absent. In some of the experiments, 

 especially those conducted with uranium, the epithelium ap- 

 peared to have undergone a shrinkage. In the later stages of 

 the nephritis when the output of urine had been reduced or an 

 anuria had developed, the epithelium, and especially that of 

 the convoluted tubules invariably showed marked alterations. 

 The epithelial changes varied with the severity of the nephritis. 



