Supplementary Material for: Impact of Peritoneal Neutrophil Extracellular Traps on Peritoneal Characteristics and Technical Failure in Patients Undergoing Peritoneal Dialysis

Introduction: Peritoneal dialysis (PD) is an effective home therapy for end-stage kidney disease. However, continuous exposure to PD fluids with high glucose concentration and recurrent peritonitis may lead to the activation of cellular and molecular processes of peritoneal damage, including inflammation and fibrosis. In particular, recent studies have highlighted the role of neutrophils in chronic inflammation. This study explores how neutrophil extracellular traps (NETs) affect peritoneal membrane function and contribute to technical failures in PD patients.
Methods: We conducted a prospective observational study involving 250 non-infectious and 30 acute peritonitis patients. NETs were measured using nucleosome and myeloperoxidase DNA levels in PD fluids. Monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-8 (MMP-8) were also measured to assess peritoneal inflammation and damage.
Results: A significant increase in peritoneal NETs, as determined by nucleosome and myeloperoxidase DNA levels, was observed in patients with acute peritonitis compared to patients without peritonitis. Even in non-infectious samples, NET levels were widely distributed and closely correlated with levels of MCP-1 and MMP-8. Higher levels of peritoneal NETs were closely associated with increased 4-hour dialysate/peritoneal (D/P) creatinine ratio and 1-hour D/P sodium levels, indicating a higher prevalence of fast transport and limited free water transport. These factors were associated with a higher risk of technical failure. During a mean follow-up of 34 months, 39.2% (98 patients) switched from PD to hemodialysis, with higher NET levels significantly increasing the risk by 1.9 times (95% confidence interval 1.27-2.83, p=0.020).
Conclusions: This study suggests the importance of peritoneal NETs not only as markers of acute inflammation but also as significant immunological predictors of chronic peritoneal membrane inflammation and dysfunction, and as potential risk factors for technical failure.