258 G. C. Kennedy 



between cause and effect is uncertain. Wilson and Byrom 

 (1939, 1941) showed that the production of hypertension by 

 "cHpping" one kidney could lead after a prolonged latent 

 period to pathological lesions in the other kidney. They 

 attributed these lesions to hypertension, because their 

 development seemed to be arrested and the hypertension 

 cured by removing the ischaemic kidney. Goldblatt (1947) 

 pointed out that all the lesions Wilson and Byrom had de- 

 scribed could occur spontaneously in rats without hyperten- 

 sion. More recent work, reviewed by Floyer (1957), suggests 

 that removal of the clip, so restoring some of the lost excretory 

 function, is a much better protective measure than removing 

 the ischaemic kidney, which frequently increases the hyper- 

 tension. The importance of extrarenal or renoprival factors 

 in producing permanent hypertension now seems well estab- 

 lished and certainly fits with our experience, and apparently 

 with Goldblatt' s, that hypertension and vascular changes are 

 a late feature of the spontaneous renal disease of rats. 



Much remains to be done, but it is hoped that some pro- 

 gress has been made towards establishing the thesis, stated at 

 the beginning of this paper, that the essential vicious cycle of 

 renal disease in old age, in one species at least, is the destruc- 

 tion of surviving nephrons by overloading, after the normal 

 renal atrophy of old age has reached a critical stage. 



Summary 



The kidney of the rat, and of most mammals including man, 

 begins to atrophy while the animal is still young. Pathological 

 changes in the kidney become more frequent during involution. 

 Irregular and apparently purposeless hyperplasia of tubular 

 cells is a prominent feature of such lesions. Hyperplasia 

 occurs in the tubules of growing rats both as part of normal 

 development and as a response to a moderate increase in the 

 excretory load, but it is not normally seen after the main 

 growth of the skeleton is completed. The stimulus to normal 

 renal growth probably arises in the pituitary gland. It is 



