ESPN 50th Annual Meeting

ESPN 2017


 
Early changes in PD membrane morphology with low GDP fluids
BETTI SCHAEFER 1 MARIA BARTOSOVA 1 Peter Sallay 3 Johan VandeWalle 4 Sara Testa 5 Rafael T Krmar 6 Maria Dzierzega 7 Nur Canpolat 8 DONALD FRASER 2 CLAUS P SCHMITT 1

1- CENTER FOR PEDIATRIC AND ADOLESCENT MEDICINE, University of Heidelberg
2- CARDIFF UNIVERSITY
3- 1st Dept. of Pediatrics, Semmelweis University, Budapest
4- Pediatric Nephrology, Department of Pediatrics, Ghent University Hospital
5- Pediatric Nephrology, Fondazione Ospedale Maggiore Policlinico, Milano
6- Div. of Pediatrics, Karolinska University Hospital, Huddinge
7- Institute of Pediatrics, Jagiellonian University Medical College, Krakow
8- Cerrahpasa School of Medicine, Istanbul
 
Introduction:

The impact of peritoneal dialysis (PD) on membrane integrity and function is incompletely understood, peritoneal changes associated with low GDP fluid usage are largely unknown. Experimental studies indicate a pivotal role of the microvasculature for transport, respective human data is scant.

Material and methods:

We obtained 212 standardized peritoneal and 153 omental specimens from 111 children at time of catheter insertion and from 99 children on PD, 84 treated with low GDP fluids for automated quantitative morphometric and molecular tissue analyses.

Results:

The mesothelial cell layer vanished with time on PD. Median capillary density increased by 54%, endothelial surface area by 37% within one year of low GDP PD, and remained high thereafter. The submesothelial three-layer vessel configuration dissipated, lymphatic vessel density remained low. The submesothelial zone thickness increased by 45% within the first year, and slowly thereafter until ≥4 years of PD, when a 3-fold increase in submesothelial fibrosis was observed. Intraindividual comparisons in 24 children reconfirmed these findings. ASMA+, activated fibroblasts and CD45/CD68+ macrophages, VEGF and TGF-ß induced pSMAD abundance, profibrotic miR21 and endothelial mesenchymal transition increased irrespective of PD fluid GDP content. Findings were comparable in 34 patients with history of peritonitis longer than 4 weeks ago. Vasculopathy was more pronounced in children on high GDP fluids. Peritoneal microvessel density correlated with 2h D/P creatinine and D/D0 glucose at baseline (rho=0.74/0.78) and while on PD (-0.51/-0.61). By multivariate analyses vessel density predicts PD membrane function.

Conclusions:

Peritoneal membrane transport function primarily depends on microvessel density. PD fluids with low GDP content induce early inflammation, EMT, angiogenesis and submesothelial fibrosis, whereas lymphatic vessel density remains low. Minor changes develop subsequently until 4 and more years of PD. These alterations are in line with inferior transport function with low GDP fluids observed in clinical trials within the first months of PD but not thereafter.