BACKGROUND Acute tubular necrosis (ATN) is the most common cause of acute renal failure. It is characterized by the destruction of tubular epithelial cells. To examine apoptosis and proliferative activity of tubular cells in the course of acute tubular necrosis, we induced acute renal failure by intramuscular hypertonic glycerol injection to New Zealand White rabbits. METHODS The immunohistochemistry was done for Ki-67 and tissue-transglutaminase (tTG), and the terminal deoxynucleotidyl transferase mediated nick end labeling (TUNEL) method was performed using a total of 77 renal specimens including 29 gun biopsies and 48 nephrectomiy specimens. RESULTS Widespread tubular injury with pigment casts and interstitial hemorrhage were noted. The tubular proliferation index was increased at 2 hours after glycerol injection, and the index peaked at 3 hours. The second cell proliferation peak was noted at 3 days. Apoptotic cells were identified by TUNEL and tTG staining. The apoptotic index was significantly increased, and it peaked at 24 hours after glycerol injection. There was a significant correlation between the proliferation index (MIB-1) the and the apototic index (TUNEL)(p= 0.001). A DNA ladder pattern was observed at 6 to 8 hours. CONCLUSIONS Tubular cell proliferation and apoptosis occur in the early phase after the induction of acute tubular necrosis, and the excess hyperplastic epithelial cells appear to be eliminated by apoptosis.
Acute tubular necrosis is a major cause of acute renal failure. Acute renal failure that is caused by crystal deposition can result from drug toxicity, lymphoplasmacytic neoplasms, ingestion of industrial organic solvents, or intratubular obstruction due to degenerated red blood cells and red blood cell casts. We herein present an uncommon case of acute renal failure in a 57-year-old woman showing an unusually massive accumulation of variable-sized, round, ellipsoid or rhomboid, pale-pink, refractile bodies in the proximal and distal tubular epithelial cells, interstitial macrophages and Bowman's spaces. These bodies were electron dense with a maximum diameter of 3 micrometer. The information we gathered from the patient history, the laboratory data and the various histochemical and immunohistochemical analyses failed to reveal the exact nature of these crystal-like structures.