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      Interstitial Fibrosis Restricts Osmotic Water Transport in Encapsulating Peritoneal Sclerosis

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          Abstract

          Encapsulating peritoneal sclerosis (EPS) is a rare but severe complication of peritoneal dialysis (PD) characterized by extensive fibrosis of the peritoneum. Changes in peritoneal water transport may precede EPS, but the mechanisms and potential predictive value of that transport defect are unknown. Among 234 patients with ESRD who initiated PD at our institution over a 20-year period, 7 subsequently developed EPS. We evaluated changes in peritoneal transport over time on PD in these 7 patients and in 28 matched controls using 3.86% glucose peritoneal equilibration tests. Compared with long-term PD controls, patients with EPS showed early loss of ultrafiltration capacity and sodium sieving before the onset of overt EPS. Multivariate analysis revealed that loss of sodium sieving was the most powerful predictor of EPS. Compared with long-term PD control and uremic peritoneum, EPS peritoneum showed thicker submesothelial fibrosis, with increased collagen density and a greater amount of thick collagen fibers. Reduced osmotic conductance strongly correlated with the degree of peritoneal fibrosis, but not with vasculopathy. Peritoneal fibrosis was paralleled by an excessive upregulation of vascular endothelial growth factor and endothelial nitric oxide synthase, but the expression of endothelial aquaporin-1 water channels was unaltered. Our findings suggest that an early and disproportionate reduction in osmotic conductance during the course of PD is an independent predictor of EPS. This functional change is linked to specific alterations of the collagen matrix in the peritoneal membrane of patients with EPS, thereby validating the serial three-pore membrane/fiber matrix and distributed models of peritoneal transport.

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          Author and article information

          Journal
          J Am Soc Nephrol
          J. Am. Soc. Nephrol
          jnephrol
          jnephrol
          ASN
          Journal of the American Society of Nephrology : JASN
          American Society of Nephrology
          1046-6673
          1533-3450
          October 2015
          30 January 2015
          : 26
          : 10
          : 2521-2533
          Affiliations
          [* ]Division and Laboratory of Nephrology, Cliniques Universitaires Saint-Luc, Institute of Experimental and Clinical Research, Université Catholique de Louvain Medical School
          []Imaging Platform, Institute of Experimental and Clinical Research, and
          []School of Public Health, Université Catholique de Louvain Medical School, Brussels, Belgium; and
          [§ ]Institute of Physiology, Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
          Author notes
          Correspondence: Dr. Olivier Devuyst, Institute of Physiology, Zurich Center for Integrative Human Physiology, University of Zurich, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland, or Dr. Eric Goffin, Division of Nephrology, Cliniques Universitaires Saint-Luc, Avenue Hippocrate 10, B 1200 Brussels, Belgium. Email: olivier.devuyst@ 123456uzh.ch or eric.goffin@ 123456uclouvain.be

          O.D. and E.G. co-directed the study and are co-senior authors.

          Article
          PMC4587704 PMC4587704 4587704 2014090939
          10.1681/ASN.2014090939
          4587704
          25636412
          6bfc4ee6-de6d-4376-845d-402b0eb4b8d6
          Copyright © 2015 by the American Society of Nephrology
          History
          : 27 September 2014
          : 24 December 2014
          Page count
          Pages: 13
          Categories
          Clinical Research
          Custom metadata
          October 2015

          peritoneal dialysis,water channels,ultrafiltration,vascular endothelial growth factor

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