Microdissection studies of the structural alterations induced in rat kidneys by experimental postischemic acute renal failure.

A unique opportunity presented itself for a morphologic study of experimental unilateral acute renal failure (ARF) in male rats. The ARF had been induced in the rats by temporary occlusion (1h) of the left renal artery. Twenty-nine rats were divided into subsets as follows: 2-3 h, 24 h, 1 week, 2, 4, 8, and 12 weeks following release of occlusion. Microdissection showed a heterogeneous population of abnormally structured proximal tubules in which the regressive lesions of tubular necrosis were combined with the progressive reaction of repair. The lesions demonstrated are reminiscent of those which have been described in ARF in the human and in experimental animals. Many proximal tubules in the 2- to 3-hour subset presented 1-3 disruptive lesions (DLs) while greater numbers of proximal tubules from the 24-hour group presented 1-5 DLs. Many proximal tubules presented no DLs, but nearly all from the 24-hour subset (97-100%) displayed a squamate appearance which paralleled and was caused by acute tubular necrosis. At 1 week, a dilated pars recta was common, but by this time, the squamate pattern had disappeared. Many casts were present. At 2 weeks, many fewer casts were present in proximal tubules and none were seen at 4, 8 or 12 weeks. The nephrons, particularly the proximal tubules, presented a variety of structural alterations at 2, 4, 8 and 12 weeks. Changes of special interest include (1) the presence of swan-necks; (2) a distinctive squamate appearance of the proximal tubules in the animals killed at 24 h; (3) a spiral, curled appearance caused by differential hyperplasia in animals at 4, 8 and 12 weeks, and (4) a tendency for ischemic lesions to involve all layers of the renal cortex.

Hydrocortisone-induced cystic metanephric maldevelopment in serum-free organ culture.

To investigate the basic pathophysiology of renal cystic maldevelopment, the production of renal cysts was studied in a newly developed murine metanephric organ culture system. In this isolated, nonvascularized system, the addition of hydrocortisone (1.4 X 10(-5) M) to completely characterized, serum-free growth medium produced striking tubular cystic abnormalities. As nephron obstruction did not occur in the nonperfused organ culture system in which neither glomerular filtration nor urine flow were present, the model experimentally isolated the roles of tubular cell metabolism and tubular wall extracellular matrix development in the production of cystic alterations. Analysis with the techniques of intact nephron microdissection and light and electron microscopy demonstrated that organ culture cysts developed in proximal tubules amid a normal background of organotypic tubular differentiation and glomerular epithelial development. Frank cystic development in the system was regularly preceded by ultrastructural alterations in and around the walls of differentiating proximal tubules. Such changes consisted of basolateral intercellular spreading which increased with progressive tubular dilation and irregular thickening and lamellation of tubular basal laminae. The ultrastructural features of the model suggest roles for hydrocortisone-induced alterations in both tubular transport processes and basal lamina structure in the experimental production of cysts. We conclude that the production of cystic changes in organ culture by hydrocortisone permits highly controlled study of the roles of altered tubular cell and basal lamina metabolism in the pathogenesis of cystic metanephric maldevelopment.