256 G. C. Kennedy 



animal at operation, and in fact the age at which the final 

 breakdown occurred was almost constant. To take the 

 extreme case, rats over a year old frequently failed to estab- 

 lish any new renal equilibrium after either type of overloading, 

 but rapidly developed pathological lesions. 



The age at which renal failure occurred was advanced still 

 further by increasing the renal loading, either by a more 

 extensive partial nephrectomy, or by combining unilateral 

 nephrectomy with overfeeding. It is sometimes said that 

 different species tolerate the removal of different proportions 

 of their renal tissue. It is difficult to see how a valid compari- 

 son can be made when the critical amount of kidney depends 

 so much on the age of the animal. We found that weanling 

 rats recovered and survived for many months after losing 

 five-sixths of their kidneys, while nine-month-old adults 

 often developed acute tubular necrosis after the same opera- 

 tion. A probable explanation for the latent period in the 

 younger animals is that it represents the time for the further 

 loss of nephrons due to ageing to reduce the available kidney 

 below the critical level. It remains to consider the part played 

 by the associated metabolic and endocrine disturbance in 

 destroying the kidney. 



Endocrine stimuli to renal hyperplasia 



A number of hormones are reno trophic. They include 

 growth hormone (White, Heinbecker and Rolff, 1949), 

 thyroid hormone (Korenchevsky and Hall, 1944) and testo- 

 sterone (Korenchevsky and Ross, 1940). The results of 

 treatment with growth hormone are particularly suggestive. 

 Acute overdosage can lead to rapid kidney destruction, but 

 treatment of a young rat for only a few days, apparently 

 causing no damage at the time, can lead to the appearance of 

 pathological lesions months later (Selye, 1951). From the 

 limited descriptions and photographs available no difference 

 can be seen between these and the spontaneous lesions of 

 older rats or those which develop after partial nephrectomy. 

 Interpretation is complicated because partial nephrectomy is 



