Effects of hypoxia on morphological and biochemical characteristics of renal epithelial cell and tubule cultures.

Apoptotic cell death plays an important role in the pathogenesis of renal atrophy in diseases of the kidney involving chronic mild ischemia. The present study constitutes an in vitro model of these diseases and assesses the modes of cell death involved after hypoxic treatment of renal epithelium. Cultures of MDCK cells or primary cultures of rat renal parenchymal tubules were treated in either a physiological or a hypoxic atmosphere. Cultures were collected before treatment and at 24 h and 48 h, for morphological and biochemical studies. Both apoptosis and necrosis were observed at significantly increased levels by 48 h of hypoxia in the MDCK cell cultures. DNA gel electrophoresis patterns supported these findings. Experiments using tubule cultures demonstrated that, during the 48 h of study, tubular epithelial cells in the center of the control tubule structures died by apoptosis, possibly as a result of mild oxygen and/or nutrient depletion. With added hypoxic treatment, however, the entire tubule structure became necrotic. Results are similar to those found during in vivo studies, thus providing in vitro models that may be developed further to define factors in the pathogenesis of some renal diseases.