#5664 PERITONEAL DIFFUSE PODOPLANIN EXPRESSION IS ASSOCIATED WITH SEVERE ARTERIOLOPATHY IN CHILDREN ON PERITONEAL DIALYSIS

Abstract Background and Aims Podoplanin is a transmembrane glycoprotein binding chemokines modulating inflammatory reactions. In healthy peritoneum, it expressed in mesothelial cells lymphatic endothelium, expression beyond these structures (diffuse podoplanin staining, DPS) has been observed adult patients with encapsulating peritoneal sclerosis (EPS). Method Parietal tissues from 71 children on PD fluids low glucose degradation product (GDP) content underwent digital histomorphometry. DPS pathomechanisms of membrane transformation vasculopathy were hierarchically clustered. A panel 13 cell markers was selected tissue sections stained metal conjugated antibodies acquired using imaging mass cytometry (IMC; Hyperion Imaging System®). After single-cell segmentation, spillover correction, normalization, types identified manual gating to train random forest classifier for final type identifications published workflows. Single-cell analysis used characterize positive signals. Results present 22% the patients, all devoid any clinical, radiological or histological feature EPS. younger, had higher dialytic exposure (median 103 vs. 154 g/m²/day, p = 0.002), lower arteriolar lumen vessel (L/V) ratio, i.e. exhibited more narrowing. duration [median 20 (14.5, 48) months] peritonitis incidence similar as non-DPS patients. multivariable analysis, exposure, duration, epithelial-to-mesenchymal transformed (EMT) patient body surface area (BSA) independently predicted presence DPS. coverage L/V ratio. subgroups matched BSA, (0.44 ± 0.13 0.31 0.18, 0.003) submesothelial CD45 leucocyte, CD68 macrophage EMT count. Submesothelial lipopolysaccharide hyaluronic acid receptor CD44 increased hyaluronan synthase 1 2 similar. Among intensity grade those history bacterial fungal (7 out 15). Two three four episodes respectively, their pattern did not differ only one episode. Hierarchical clustering demonstrated highest similarity areas areas. IMC areas, signals derived M2 classified macrophages (CD68+CD163+) fibroblastic [αSMA positive/non-endothelial/non-macrophage (αSMA+PROX1-CD31-CD68-CD163-)], M1 (CD68+CD163-) lowest. Conclusion Peritoneal pediatric low-GDP associated infectious invasion, predicts obliterating vasculopathy. We major source extra-lymphatic accumulation, suggesting role severe transformation.