Taming Apoptosis in Peritoneal Dialysis

Abstract

Excessive, insufficient, or untimely apoptosis may result in disorders of cell numbers. Peritoneal demesothelization is an example of disease by decreased cell number; untimely leukocyte apoptosis impairs peritoneal defense. Conventional peritoneal dialysis solutions accelerate neutrophil apoptosis. Glucose degradation products such as 3,4-dideoxyglucosone-3-ene (3,4-DGE) decisively contribute to apoptosis induced by these solutions, in both leukocytes and mesothelial cells and in both culture and peritoneal dialysis patients. Pan-caspase inhibition retards neutrophil apoptosis and improves peritoneal clearance of Staphylococcus aureus in animal models. However, regulation of apoptosis in mesothelial cells is more complex than in leukocytes, and caspase inhibitors may not be the optimal drugs to modulate apoptosis in these cells. In this regard, Bax antagonistic peptides protect mesothelial cells from 3,4-DGE. In addition, novel molecular targets have been identified. Short-term modulation of apoptosis may be useful to accelerate recovery and to prevent irreversible peritoneal injury following peritonitis.