The aim of this research proposal is to investigate the adaptive functional and structural response of the deep nephron population to renal mass ablation in the rat. A model of unilateral cortical necrosis recently studied in our laboratory will be used for this purpose. The first part of the proposal will further characterize the cortical necrosis model both morphologically and functionally in young adult rats. The model will then be used to evaluate the adaptive functional changes and glomerular structural alterations of the deep nephron population after unilateral cortical necrosis and contralateral nephrectomy in (a) normal weanling and young adult rats, (b) rats with diabetes insipidus (DI rats), and (c) rats made moderately diabetic with streptozotocin. These three experimental models will permit us to evaluate the effects of age, lack of nephron heterogeneity, and pre-existing glomerular injury, respectively on the adaptive response of the deep nephron population to renal mass ablation. The influence of dietary protein intake on this adaptive response will also be examined in each of the three experimental conditions. Clearance and micropuncture methods, the ferrocyanide technique, microangiography, and light and transmission electron microscopy will be used in these studies. It is hoped that the cortical necrosis model will provide important information concerning the role of the deep nephron population in the development and progression of focal glomerular sclerosis, a primary glomerular disease affecting both children and adults.
