The effect of peritoneal dialysates with low-glucose degradation products on peritoneal membrane morphology is largely unknown, with functional relevancy predominantly derived from experimental studies. To investigate this, we performed automated quantitative histomorphometry and molecular analyses on 256 standardized peritoneal and 172 omental specimens from 56 children with normal renal function, 90 children with end-stage kidney disease at time of catheter insertion, and 82 children undergoing peritoneal dialysis using dialysates with low-glucose degradation products. Follow-up biopsies were obtained from 24 children after a median peritoneal dialysis of 13 months. Prior to dialysis, mild parietal peritoneal inflammation, epithelial-mesenchymal transition and vasculopathy were present. After up to six and 12 months of peritoneal dialysis, blood microvessel density was 110 and 93% higher, endothelial surface area per peritoneal volume 137 and 95% greater, and submesothelial thickness 23 and 58% greater, respectively. Subsequent peritoneal changes were less pronounced. Mesothelial cell coverage was lower and vasculopathy advanced, whereas lymphatic vessel density was unchanged. Morphological changes were accompanied by early fibroblast activation, leukocyte and macrophage infiltration, diffuse podoplanin presence, epithelial mesenchymal transdifferentiation, and by increased proangiogenic and profibrotic cytokine abundance. These transformative changes were confirmed by intraindividual comparisons. Peritoneal microvascular density correlated with peritoneal small-molecular transport function by uni- and multivariate analysis. Thus, in children on peritoneal dialysis neutral pH dialysates containing low-glucose degradation products induce early peritoneal inflammation, fibroblast activation, epithelial-mesenchymal transition and marked angiogenesis, which determines the PD membrane transport function.

1st Department of Pediatrics Semmelweis University Budapest Hungary

Children's Mercy Hospital Kansas City Missouri USA

Department of General Pathology Institute of Pathology University of Heidelberg Heidelberg Germany

Department of Pathology University Medical Center Mainz Mainz Germany

Department of Pediatric Nephrology and Hypertension Jagiellonian University Medical College Krakow Poland

Department of Pediatric Nephrology Faculty of Medicine Cukurova University Adana Turkey

Department of Pediatric Nephrology Hepatology and Metabolic Diseases Children's Hospital Hannover Medical School Germany

Department of Pediatric Nephrology Istanbul University Cerrahpasa Medical Faculty Istanbul Turkey

Department of Pediatric Nephrology University Children's Medical Clinic University Medical Center Hamburg Eppendorf Germany

Department of Pediatrics 1 University Hospital of Strasbourg Strasbourg France

Department of Pediatrics and Adolescent Medicine Medical University Vienna Austria

Department of Pediatrics Division of Nephrology University of Charité Berlin Germany

Department of Pediatrics Hospital Kuala Lumpur Malaysia

Department of Pediatrics University Hospital Motol Prague Czech Republic

Dialysis Unit Pediatric Nephrology and Dialysis Division IRCCS Giannina Gaslini Institute Genoa Italy

Division of Nephrology Department of Pediatrics University of Alabama at Birmingham Birmingham Alabama USA

Division of Pediatric Nephrology Center for Pediatric and Adolescent Medicine University of Heidelberg Germany

Division of Pediatric Surgery Department of General Visceral and Transplantation Surgery University of Heidelberg

Division of Pediatrics Department for Clinical Science Intervention and Technology Karolinska Institute Karolinska University Hospital Huddinge Stockholm Sweden

KfH Pediatric Kidney Center Department of Pediatric Nephrology University of Marburg Marburg Germany

Pediatric Nephrology Children's and Adolescent's Hospital University Hospital of Cologne Germany

Pediatric Nephrology Dialysis and Transplantation Unit Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano Italy

Pediatric Nephrology Hospital Universitario Vall d' Hebrón Universitat Autonoma Barcelona Barcelona Spain

Pediatric Nephrology University Children's Hospital Essen Germany

Pediatric Nephrology Utopaed Department of Pediatrics Ghent University Hospital Belgium

Service de Néphrologie Pédiatrique Hôpital Femme Mere Enfant Hospices Civils de Lyon Lyon France

Vilnius University Faculty of Medicine Institute of Clinical Medicine Clinic of Children's Diseases Lithuania

Kidney Int. 2018 Aug;94(2):246-248. doi: 10.1016/j.kint.2018.04.014. PubMed

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