Two related morphological studies were undertaken in rats. In the first, cellular events involved in the development of ischemic renal
atrophy induced by
renal artery stenosis were recorded. One primary objective was to document the pathogenetic role that a distinct form of cell death, termed apoptosis, played in the development of renal tubular
atrophy. A small, partially closed ligating
clip was used to produce
stenosis of the left renal artery, or a
sham operation was performed. Animals were killed 2-28 days after operation. The ensuing ischemic renal
atrophy was studied histologically and ultrastructurally, and apoptosis was counted in
paraffin sections, using established criteria for its identification. Nuclear [3H]
thymidine uptake was used as an
indicator of cell proliferation. Morphometric studies recorded changes in area of transected tubular profiles. Correlation was sought between the morphological changes, data gained by the above quantitations, and the progressive reduction in renal mass that occurred during the experiment. Our results showed that during the acute phase (2-8 days), cell death was effected by both apoptosis and
necrosis and increased tubular epithelial cell labeling and mitoses provided evidence of epithelial repair. During the chronic phase (10-28 days), when the mass of the ischemic kidney underwent significant reduction, cell death was effected by apoptosis alone, and the level of tubular epithelial cell labeling and mitosis returned to near normal. Intraepithelial macrophages were significant in removing the apoptotic bodies. Area of tubular epithelium was reduced in atrophic tubules, and it is proposed that this reduction may be explained by apoptotic cell deletion, as well as cell shrinkage. In the second study, evidence of regeneration was sought in atrophic kidneys after surgical reversal of
renal artery stenosis and, in other animals, after unilateral
nephrectomy of the contralateral kidney. Our results showed that regeneration, involving both
hypertrophy and
hyperplasia, was stimulated only by removal of the hypertrophied contralateral kidney and occurred whether or not
stenosis of the renal artery was reversed.