Neutral pH and low-glucose degradation product dialysis fluids induce major early alterations of the peritoneal membrane in children on peritoneal dialysis

Schaefer B 1 , Bartosova M 1 , Macher-Goeppinger S 2 , Sallay P 3 , Vörös P 3 , Ranchin B 4 Show all authors , Vondrak K 5 , Ariceta G 6 , Zaloszyc A 7 , Bayazit AK 8 , Querfeld U 9 , Cerkauskiene R 10 , Testa S 11 , Taylan C 12 , VandeWalle J 13 , Yap Y 14 , Krmar RT 15 , Büscher R 16 , Mühlig AK 17 , Drozdz D 18 , Caliskan S 19 , Lasitschka F 20 , Fathallah-Shaykh S 21 , Verrina E 22 , Klaus G 23 , Arbeiter K 24 , Bhayadia R 25 , Melk A 25 , Romero P 26 , Warady BA 27 , Schaefer F 1 , Ujszaszi A 1 , Schmitt CP 28

Affiliations 

  • 1 Division of Pediatric Nephrology, Center for Pediatric and Adolescent Medicine, University of Heidelberg, Germany
  • 2 Department of Pathology, University Medical Center Mainz, Mainz, Germany
  • 3 First Department of Pediatrics, Semmelweis University, Budapest, Hungary
  • 4 Service de Néphrologie Pédiatrique, Hôpital Femme Mere Enfant, Hospices Civils de Lyon, Lyon, France
  • 5 Department of Pediatrics, University Hospital Motol, Prague, Czech Republic
  • 6 Pediatric Nephrology, Hospital Universitario Vall d' Hebrón, Universitat Autonoma, Barcelona, Barcelona, Spain
  • 7 Department of Pediatrics 1, University Hospital of Strasbourg, Strasbourg, France
  • 8 Department of Pediatric Nephrology Faculty of Medicine, Cukurova University, Adana, Turkey
  • 9 Department of Pediatrics, Division of Nephrology, University of Charité, Berlin, Germany
  • 10 Vilnius University Faculty of Medicine, Institute of Clinical Medicine, Clinic of Children's Diseases, Lithuania
  • 11 Pediatric Nephrology, Dialysis and Transplantation Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
  • 12 Pediatric Nephrology, Children's and Adolescent's Hospital, University Hospital of Cologne, Germany
  • 13 Pediatric Nephrology, Utopaed, Department of Pediatrics, Ghent University Hospital, Belgium
  • 14 Department of Pediatrics, Hospital Kuala Lumpur, Malaysia
  • 15 Division of Pediatrics, Department for Clinical Science, Intervention and Technology, Karolinska Institute, Karolinska University Hospital, Huddinge, Stockholm, Sweden
  • 16 Pediatric Nephrology, University Children's Hospital, Essen, Germany
  • 17 Department of Pediatric Nephrology, University Children's Medical Clinic, University Medical Center Hamburg-Eppendorf, Germany
  • 18 Department of Pediatric Nephrology and Hypertension, Jagiellonian University Medical College, Krakow, Poland
  • 19 Department of Pediatric Nephrology, Istanbul University Cerrahpasa Medical Faculty, Istanbul, Turkey
  • 20 Department of General Pathology, Institute of Pathology, University of Heidelberg, Heidelberg, Germany
  • 21 Division of Nephrology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA
  • 22 Dialysis Unit, Pediatric Nephrology and Dialysis Division, IRCCS Giannina Gaslini Institute, Genoa, Italy
  • 23 KfH Pediatric Kidney Center, Department of Pediatric Nephrology, University of Marburg, Marburg, Germany
  • 24 Department of Pediatrics and Adolescent Medicine, Medical University Vienna, Austria
  • 25 Department of Pediatric Nephrology, Hepatology and Metabolic Diseases, Children's Hospital, Hannover Medical School, Germany
  • 26 Division of Pediatric Surgery, Department of General, Visceral and Transplantation Surgery, University of Heidelberg
  • 27 Children's Mercy Hospital, Kansas City, Missouri, USA
  • 28 Division of Pediatric Nephrology, Center for Pediatric and Adolescent Medicine, University of Heidelberg, Germany. Electronic address: clauspeter.schmitt@med.uni-heidelberg.de
Kidney Int, 2018 08;94(2):419-429.
PMID: 29776755 DOI: 10.1016/j.kint.2018.02.022

Abstract

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

MeSH terms
Similar publications