Cell Death Pathways

Acute kidney injury (AKI) has been associated with higher morbidity and mortality in the critically ill. As such, there has been a growing interest in elucidating the pathophysiology behind AKI in an attempt to increase our understanding of the processes and work toward definitive therapies. Cell death is a process that can be both normal and pathologic and can be classified into two distinct categories: accidental cell death and regulated cell death. Accidental cell death results from extreme conditions and is not amenable to modulation. On the other hand, regulated cell death refers to multiple genetically encoded pathways that serve the purpose of maintaining cell homeostasis and represents important adaptive strategies. Apoptosis and regulated necrosis, both forms of regulated cell death, have been documented in both ischemic and nephrotoxic renal injury and development of AKI. This identification of multiple regulated cell death pathways has led to a greater understanding of cell death in these conditions and the development of novel mechanism-based therapies to prevent and treat AKI. In this chapter, we present a summary of the various known mechanisms of apoptosis and regulated necrosis. We discuss what is known about the mechanisms underlying regulated cell death in AKI and review some of the evidence that has been obtained in recent years. Finally, we present novel strategies targeting regulated cell death in human AKI.