The Spectrum of Podoplanin Expression in Encapsulating Peritoneal Sclerosis

Niko Braun,Martin Kimmel,M Dominik Alscher,Peter Fritz,Rudolf P Wüthrich,Joerg Latus,Seth L Alper,Ilka Edenhofer,Fabian Reimold,Dagmar Biegger,Stephan Segerer,Maja Lindenmeyer,Clemens D Cohen

doi:10.1371/journal.pone.0053382

Abstract

Encapsulating peritoneal sclerosis (EPS) is a life threatening complication of peritoneal dialysis (PD). Podoplanin is a glycoprotein expressed by mesothelial cells, lymphatic endothelial cells, and myofibroblasts in peritoneal biopsies from patients with EPS. To evaluate podoplanin as a marker of EPS we measured podoplanin mRNA and described the morphological patterns of podoplanin-positive cells in EPS. Included were 20 peritoneal biopsies from patients with the diagnosis of EPS (n = 5), patients on PD without signs of EPS (n = 5), and control patients (uremic patients not on PD, n = 5, non-uremic patients n = 5). EPS patient biopsies revealed significantly elevated levels of podoplanin mRNA (p<0.05). In 24 peritoneal biopsies from patients with EPS, podoplanin and smooth muscle actin (SMA) were localized by immunohistochemistry. Four patterns of podoplanin distribution were distinguishable. The most common pattern (8 of 24) consisted of organized, longitudinal layers of podoplanin-positive cells and vessels in the fibrotic zone (“organized” pattern). 7 of 24 biopsies demonstrated a diffuse distribution of podoplanin-positive cells, accompanied by occasional, dense clusters of podoplanin-positive cells. Five biopsies exhibited a mixed pattern, with some diffuse areas and some organized areas ("mixed"). These contained cuboidal podoplanin-positive cells within SMA-negative epithelial structures embedded in extracellular matrix. Less frequently observed was the complete absence of, or only focal accumulations of podoplanin-positive fibroblasts outside of lymphatic vessels (podoplanin “low”, 4 of 24 biopsies). Patients in this group exhibited a lower index of systemic inflammation and a longer symptomatic period than in EPS patients with biopsies of the "mixed" type (p<0.05). In summary we confirm the increased expression of podoplanin in EPS, and distinguish EPS biopsies according to different podoplanin expression patterns which are associated with clinical parameters. Podoplanin might serve as a useful adjunct to the morphological workup of peritoneal biopsies.

Highlights

Encapsulating peritoneal sclerosis (EPS) is a rare, but lifethreatening complication of long-term peritoneal dialysis (PD) [1,2,3]
Fibrin deposits may lead to adhesions and permanent scarring, eventually resulting in bowel obstruction
The previously described accumulation of podoplanin-positive myofibroblasts in EPS was associated with significant induction of podoplanin mRNA expression [10,11]

Summary

Introduction

Encapsulating peritoneal sclerosis (EPS) is a rare, but lifethreatening complication of long-term PD [1,2,3]. The diagnosis is based on the combination of clinical symptoms (bowel obstruction), radiological findings (suggesting extensive thickening of the peritoneal membrane as the cause of bowel obstruction), and/or the histo-morphological picture [1]. Peritoneal biopsy histomorphological features pathognomonic for EPS have not been defined, and the importance of peritoneal biopsy in the clinical diagnosis of EPS remains poorly established. Morphological signs such as mesothelial denudation, extreme fibrotic thickening, peritoneal fibroblast swelling, interstitial fibrosis, angiogenesis with increased capillary density, and mononuclear cell infiltration are all typical for EPS, but not specific [5,6,7]. Fibrin deposits may lead to adhesions and permanent scarring, eventually resulting in bowel obstruction

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