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Background <p>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.</p> Methods <p>Forty-five children were enrolled in the International Pediatric Peritoneal Biobank. Peritoneal biopsies taken at PD initiation and after ≥ 12&#xa0;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&#xa0;months were assayed for cell-free DNA, NET proteins, DNase1, and DNase1L3.</p> Results <p>After chronic PD, the peritoneum displayed doubled microvessel density, tripled submesothelial thickness, and marked immune-cell infiltration (all <i>p</i> &lt; 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 (<i>p</i> &lt; 0.05). DNase1 levels correlated with membrane thickness (<i>r</i> = 0.46, <i>p</i> = 0.003) and DNase1L3 with vascular density (<i>r</i> = 0.51, <i>p</i> = 0.001), suggesting limited compensatory NET clearance.</p> Conclusions <p>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.</p> Graphical Abstract <p></p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月18日

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  • Charlotte Maria Dücker,
  • Martin Herrmann,
  • Susanne Boettcher,
  • Sarah Bauer-Carmona,
  • Raphael-Sebastian Schild,
  • Lavinia Schönfeld,
  • Laia Pagerols Raluy,
  • Konrad Reinshagen,
  • Claus Peter Schmitt,
  • Maria Bartosova Medvid,
  • Michael Boettcher

摘要

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.

Graphical Abstract