The peritoneal immune niche in peritoneal dialysis-induced membrane failure: macrophages, neutrophils and extracellular trap biology.

Peritoneal dialysis (PD) is associated with progressive remodeling of the peritoneal membrane, with fibrosis, vasculopathy, and transport deterioration that culminate in ultrafiltration failure (UFF); a smaller subset of patients progresses to encapsulating peritoneal sclerosis (EPS). Myeloid-driven sterile inflammation is a central feature of this process, yet the evidence base differs sharply across the immune actors implicated. In this Perspective, we evaluate that evidence through a three-layer framework separating PD-direct data from non-PD peritoneal injury data and other-organ analogies. Macrophages are the best-established organizers of peritoneal niche remodeling. Neutrophils are well characterized in peritonitis but only gradually appear in chronic non-infectious functional disorders. Among extracellular traps, neutrophil extracellular traps (NETs) carry the strongest PD-specific signal: effluent proxies are linked to membrane transport phenotype and risk for technical failure. Macrophage extracellular traps (METs) rest on a single PD-specific mechanistic study and preliminary conference-level human data. We propose that chronic PD exposure conditions this niche and that second-hit inflammatory events (such as peritonitis) accelerate injury. If extracellular trap formation proceeds faster than nuclease- and macrophage-mediated clearance, trap-derived extracellular DNA may persist in the peritoneal cavity. We further hypothesize that, after uptake by bystander cells, cytosolic DNA sensing through cGAS-STING is engaged and may amplify membrane failure.