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Apoptotic mechanisms in acute renal failure
N Ueda1, G P Kaushal, S V Shah
1Department of Medicine, University of Arkansas for Medical Sciences, and Central Arkansas Veterans Healthcare System, Little Rock 72205, USA.
Abstract:
It has been generally accepted that a catastrophic breakdown of regulated cellular homeostasis, known as necrosis, is the mode of cellular injury in various forms of acute renal failure. One of the major advances in our understanding of cell death has been the recognition that the pathways traditionally associated with apoptosis as described in the landmark study by Kerr, Wyllie, and Currie in 1972 maybe very critical in the form of cell injury associated with necrosis. The pathway that is followed by the cell varies with both nature and severity of insults and may evolve from an apoptotic to a necrotic form of cell death. It is also likely that there are some common pathways that are shared and regulated in the two modes of cell death. In this review, we first describe evidence for the role of apoptotic pathways in ischemic acute renal failure, and then consider the potential mechanisms that may participate in this model of acute renal tubular injury. We then summarize the current information of apoptotic pathways related to other common causes of acute renal failure including endotoxin-induced, toxic acute renal failure and transplant rejection. A better understanding of the mechanisms of apoptosis could lead to safer and more specific therapeutic interventions for acute renal failure.
Insights
Cell death pathways, including apoptosis, play a critical role in acute renal failure. Understanding these mechanisms can lead to targeted therapies for kidney injury.
Area of Science:
- Nephrology
- Cell Biology
- Pathology
Background:
- Acute renal failure is traditionally linked to necrosis, a breakdown of cellular homeostasis.
- Recent research highlights the significant role of apoptosis in cellular injury, even in necrosis.
- Cellular death pathways can shift from apoptotic to necrotic forms depending on the insult.
Purpose of the Study:
- To review the evidence for apoptotic pathways in ischemic acute renal failure.
- To explore potential mechanisms of apoptosis in acute tubular injury.
- To summarize current knowledge on apoptosis in other causes of acute renal failure.
Main Methods:
- Literature review of studies on apoptosis and acute renal failure.
- Analysis of cellular injury mechanisms in various forms of acute kidney injury.
- Synthesis of information on apoptotic pathways in ischemic, endotoxin-induced, toxic, and transplant-related renal failure.
Main Results:
- Apoptotic pathways are implicated in ischemic acute renal failure.
- Common regulatory pathways may exist between apoptosis and necrosis.
- Apoptosis is relevant to endotoxin-induced, toxic, and transplant rejection-related acute renal failure.
Conclusions:
- Apoptosis is a critical component of acute renal failure, not just necrosis.
- Further understanding of apoptotic mechanisms can inform therapeutic strategies.
- Targeting apoptosis offers potential for safer and more specific treatments for acute kidney injury.