Role of apoptosis of renal tubular cells in acute renal failure: Therapeutic implications

Acute renal failure (ARF) can be defined as a sudden loss of renal function and is a common and serious clinical problem. There are many causes of ARF but the most common cause results from injury to the renal tubular epi-the lial cells (RTECs). RTECs can be injured by schemia or by cytotoxic agents and, once injured, can die by necrosis or apotosis. In general, necrosis oc curs in response to any severe injury, which leads to the biochemical colla pse of the cell. Milder forms of the same types of injury cause apoptosis. At the cellular level there are fundamental differences between necrosis an d apoptosis. Necrosis results from the additive effect of a number of indep endent biochemical events that are activated by severe depletion of cell en ergy stores. By contrast, apoptosis occurs via a coordinated, predictable a nd pre-determined pathway. These biochemical differences between apoptosis and necrosis have important therapeutic implications. Once a cell has been severely injured, necrosis is difficult to prevent. By contrast, the apopto tic pathway can potentially be modulated to maintain cell viability. The co mponents of the apoptotic pathway that are potentially amenable to therapeu tic modulation are discussed in detail in this review.