Eryptosis in Peritoneal Dialysis-Related Peritonitis: The Potential Role of Inflammation in Mediating the Increase in Eryptosis in PD.

Background: Peritonitis and exit site infections are the main complications of patients treated with peritoneal dialysis (PD). Erythrocytes (red blood cells­RBCs) are very sensitive cells, and they are characterized by eryptosis (programmed cell death). The purpose of this research was to assess eryptosis in PD patients with PD-related peritonitis and its connection to inflammatory markers in vivo and in vitro. Material and Methods: In this study, we included 65 PD patients: 34 PD patients without systemic inflammation nor PD-related peritonitis in the previous 3 months, and 31 PD patients with an acute episode of PD-related peritonitis. We measured C-reactive protein (CRP) and cytokine (IL-1ß, IL-6, and IL-18) levels as systemic inflammatory markers. Eryptosis was evaluated by flow cytometric analyses in freshly isolated RBCs. The induction of eryptosis due to in vitro exposure to IL-1ß, IL-6, and IL-18 was verified. Results: Eryptosis was significantly higher in PD patients with peritonitis (9.6%; IQR 4.2−16.7), compared to the those in the other group (2.7%; IQR 1.6−3.9) (p < 0.0001). Significant positive correlations were noticed between eryptosis and CRP, IL-1ß, and IL-6. RBCs, incubated with greater concentrations of all cytokines in vitro, resulted in significantly higher occurrences of eryptosis in comparison with those incubated with lower concentration and with untreated cell (p < 0.05), and for those with extensive exposure (p < 0.05). Conclusion: In conclusion, we investigated a potential relationship between systemic eryptosis and the in vivo and in vitro inflammatory damage of the peritoneal membrane during peritonitis. Thus, the presented results revealed that upregulated inflammatory markers and immune system dysregulation could be the cause of high levels of systemic eryptosis during PD-related peritonitis.