Regulation of renal tubular cell apoptosis and proliferation after ischemic injury to a solitary kidney

The time course and regulation of apoptosis and cellular regeneration after 30 minutes of acute ischemic injury to a single kidney was elucidated in rats at five time points over 20 weeks. The fraction of apoptotic cells was most prominent at 1 day after the insult in the distal tubule (8% +/- 4% vs. 0% +/- 0%, acute renal failure (ARF) vs sham, respectively) and was still elevated at 7 days (2% +/- 2% vs 0% 0%). At that time, the whole kidney mRNA expression of the apoptosis inhibitory genes bcl-xL and bcl-2, as well as that of the apoptosis promotor box, was significantly reduced. Immunohistochemistry of kidney specimen showed suppression of bcl-2 in the distal tubule but up-regulation in the proximal tubule, whereas bax protein was more strongly expressed in the distal tubule. Cellular proliferation started at day 1 and continued over the following 20 weeks, leading to severe tubular dilation and kidney failure. These data indicate that differential regulation of bcl-2 family members contributes to the early apoptotic clearance of lethally injured tubular epithelial cells after ischemic injury to a solitary kidney.