254 G. C. Kennedy 



The pathological renal changes in old rats are almost in- 

 variably accompanied by great enlargement of the adrenals, 

 frequently by parathyroid hyperplasia, and in the later 

 stages, at least, by cardiac hypertrophy and hypertension. 

 Before considering further which is cause and which is effect, 

 a description will be given of a number of ways in which 

 similar renal lesions can be produced in much younger rats in 

 association with the same endocrine and vascular changes. 



"Senile" changes after renal overloading 

 in younger rats 



The first condition in which these lesions were found in 

 fairly young rats was in experimental hypothalamic obesity. 

 When the ventromedial part of the hypothalamus is des- 

 troyed electrolytically, the appetite of a rat may be doubled 

 for several weeks and the animal becomes grotesquely fat. In 

 view of the association of clinical obesity with renal disease 

 and hypertension, it is interesting that most of these fat rats 

 developed typical senile kidney lesions about nine months 

 earlier than unoperated controls (Kennedy, 1951). If the 

 animals were operated on at three months old, they survived 

 nine to 12 months before pathological lesions appeared in the 

 kidneys, but the kidneys became enlarged during the period 

 of overfeeding soon after the hypothalamic puncture. Moise 

 and Smith (1927) and Addis and Oliver (Oliver, 1945) showed 

 that the renal enlargement produced by a high protein diet 

 in rats could eventually cause pathological changes, and it 

 seemed possible that this might be the way in which the kid- 

 neys were damaged in hypothalamic overfeeding. As a first 

 step an examination was made of the chemical changes in the 

 kidneys during the earlier stages of development of the 

 obesity, while the food intake was very high. In Table II 

 these are compared with the changes found previously in the 

 surviving kidneys after unilateral nephrectomy, and they 

 followed an almost identical pattern. This suggested a con- 

 venient way to isolate the effect of simple kidney overloading 

 during overfeeding from any possible effect of the subsequent 



