Ultrastructural Changes and Nestin Expression Accompanying Compensatory Renal Growth After Unilateral Nephrectomy in Adult Rats

Abstract

BackgroundGlomerular podocytes form the final barrier against protein loss and are affected by many of renal diseases. Nestin is an intermediate filament protein originally described in neural stem cells and is recently thought to be expressed in differentiated podocytes of the adult kidney, which might be associated with the maintenance of the foot process structure. Unilateral nephrectomy in adult animals results in compensatory structural and functional changes. It is an adaptive response to the increased functional demand in order to maintain homeostasis of fluid and solutes. The study of the ultrastructural and histopathological changes particularly those concerned with the podocytes are few in literature. The aim of this work is to assess the renal histopathological changes on the ultrastructural level in the adapted kidney at different time intervals following unilateral nephrectomy in adult rats.MethodologyFemale white rats of same age and weight (n = 48 weight 200–250 g) were divided into four groups (n = 12 each); Group I (control naïve rats) and Groups II, III, IV where unilateral nephrectomy was performed on days 10, 20 and 30 respectively (sham operated rats were included in each group). Left unilateral nephrectomy in all groups was performed using a midline abdominal incision. Rats were sacrificed and the right kidneys were removed at days (10d, 20d and 30d). Each nephrectomy specimen was decapsulated, blotted dry, and weighed. Kidney sections from each specimen were subjected to H&E examination, transmission electron microscopic study (TEM) as well as immunostain using the intermediate filament protein Nestin.ResultsNo difference was found between kidney sections from the control group and the sham operated groups. A significant increase in the weight of the right kidneys was noted in 20d and 30d nephrectomized groups (P < 0.001). The ultrastructural adaptive changes seen in the glomeruli on day 10 were subsequently reduced in the 20d, and 30d groups. This finding corresponded to a similar pattern of Nestin expression in the podocytes, which showed significant increase in day 10 followed by reduced expression in day 20 and day 30 groups. Histopathological evaluation of the 10d group showed signs of kidney injury in the form of widening of Bowman's space and shrunken glomeruli. On TEM, kidneys in this group showed disrupted minor processes of the podocytes with irregular nuclei and numerous lysosomes. On the other hand, animals sacrificed at 20days showed markedly reduced renal adaptive changes in the form of thickening of the basement membrane and widened subpodocytic space with loss of microvilli of the lining of proximal convoluted tubules. Similar changes were also noted in the 30d group. As for Nestin, its expression was found significantly higher in the 10d group compared to the 20d and 30d groups. It was also higher in the 30d group compared to the control group.ConclusionThe correlation between the ultrastuctural changes and Nestin expression confirms that this intermediate filament protein is important for increasing the mechanical stability of the podocytes in order to enable them to undergo morphological changes in response to the tensile glomerular capillary wall. However, further studies investigating more remote ultrastructural changes and their relation with Nestin expression are needed to confirm this relationship.