Neutrophil extracellular traps drive peritoneal inflammation and tissue remodeling in pediatric peritoneal dialysis.

Abstract

Background: Peritoneal dialysis (PD) sustains children with chronic kidney disease stage 5 (CKD5) but promotes peritoneal membrane remodeling. Neutrophil extracellular traps (NETs) orchestrate antimicrobial defense and sterile inflammation; their involvement in PD-induced transformation is unknown.

Methods: Forty-five children were enrolled in the International Pediatric Peritoneal Biobank. Peritoneal biopsies taken at PD initiation and after ≥ 12 months of low-glucose-degradation-product PD were compared with surgical biopsies from non-uremic peers. Histomorphometry quantified microvessel density, submesothelial thickness, leukocyte infiltration, collagen I/III, and NET markers (citrullinated histone H3, neutrophil elastase, myeloperoxidase). Dialysate and plasma collected every 2 months for 18 months were assayed for cell-free DNA, NET proteins, DNase1, and DNase1L3.

Results: After chronic PD, the peritoneum displayed doubled microvessel density, tripled submesothelial thickness, and marked immune-cell infiltration (all p < 0.01). NET structures were prominent in tissue, while dialysate and plasma concentrations of cell-free DNA, citrullinated histone H3, neutrophil elastase, and myeloperoxidase increased two- to fourfold versus baseline (p < 0.05). DNase1 levels correlated with membrane thickness (r = 0.46, p = 0.003) and DNase1L3 with vascular density (r = 0.51, p = 0.001), suggesting limited compensatory NET clearance.

Conclusions: Chronic PD elicits NET-driven sterile inflammation that parallels structural remodeling of the pediatric peritoneum. Supplementing PD fluids with exogenous NET-degrading enzymes may preserve membrane integrity and prolong PD suitability in children.