MECHANISMS OF APOPTOSIS AND ITS POTENTIAL ROLE IN RENAL TUBULAR EPITHELIAL-CELL INJURY

Cells can die by two distinct pathways: apoptosis or necrosis. Necrosi s is associated with rapid metabolic collapse that leads to cell swell ing, early loss of plasma membrane integrity, and ultimate cell ruptur e. Cytosolic contents leak from the necrotic cell causing injury and i nflammation to surrounding tissue. In contrast, apoptosis is an energy -requiring, gene-directed process, which, when activated, results in c ell ''suicide.'' The morphological and biochemical characteristics of cells dying by apoptosis differ markedly from those of cells dying by necrosis. During apoptosis, cells decrease in size and round up. The n uclear chromatin undergoes condensation and fragmentation. The apoptot ic cell then breaks apart into many plasma membrane-bound vesicles cal led ''apoptotic bodies, which contain fragments of condensed chromatin and morphologically intact organelles such as mitochondria. Apoptotic cells and bodies are rapidly phagocytosed, thereby protecting surroun ding tissues from injury. The rapid and efficient clearance of apoptot ic cells makes apoptosis extremely difficult to detect in tissue secti ons. Recent studies show that multiple cytotoxic stimuli well known to cause necrosis can lead to apoptosis instead when cells are exposed t o the same noxious agents at lower concentrations. This insight has le d to an interest in the role of apoptosis in the pathogenesis of renal diseases that result primarily from injury to renal tubular epithelia l cells. These diseases include acute and chronic renal failure from e xposure of the kidney to ischemia or to cytotoxic agents. In this revi ew we discuss some relevant aspects of the differences between necroti c and apoptotic cell death. We also present evidence to support the hy pothesis that apoptosis is an important pathogenic mechanism in those forms of acute and chronic renal failure in which the renal tubular ep ithelial cell is the primary target of ischemic or toxic injury.