Vascular Endothelial Cell Injury Is an Important Factor in the Development of Encapsulating Peritoneal Sclerosis in Long-Term Peritoneal Dialysis Patients

<div><p>Background and Objectives</p><p>Encapsulating peritoneal sclerosis (EPS) is a rare but serious and life-threatening complication of peritoneal dialysis (PD). However, the precise pathogenesis remains unclear; in addition, predictors and early diagnostic biomarkers for EPS have not yet to be established.</p><p>Methods</p><p>Eighty-three peritoneal membrane samples taken at catheter removal were examined to identify pathological characteristics of chronic peritoneal deterioration, which promotes EPS in patients undergoing long-term PD treatment with low occurrence of peritonitis.</p><p>Results</p><p>According to univariable logistic regression analysis of the pathological findings, thickness of the peritoneal membrane (<i>P</i> = 0.045), new membrane formation score (<i>P</i> = 0.006), ratio of luminal diameter to vessel diameter (L/V ratio, <i>P</i><0.001), presence of CD31-negative vessels (<i>P</i> = 0.021), fibrin deposition (<i>P</i><0.001), and collagen volume fraction (<i>P</i> = 0.018) were associated with EPS development. In analyses of samples with and without EPS matched for PD treatment period, non-diabetes, and PD solution, univariable analysis identified L/V ratio (per 0.1 increase: odds ratio (OR) 0.44, <i>P</i> = 0.003) and fibrin deposition (OR 6.35, <i>P</i> = 0.027) as the factors associated with EPS. L/V ratio was lower in patients with fibrin exudation than in patients without fibrin exudation.</p><p>Conclusions</p><p>These findings suggest that damage to vascular endothelial cells, as represented by low L/V ratio, could be a predictive finding for the development of EPS, particularly in long-term PD patients unaffected by peritonitis.</p></div

Representative pathological findings of severe peritonitis, which is associated with fibrin exudation.

<p>Fungal peritonitis (<b>A</b>-<b>D</b>), <i>Pseudomonas aeruginosa</i> peritonitis (<b>E</b>, <b>F</b>), and <i>Serratia marcescens</i> peritonitis (<b>G, H</b>) show exudation of fibrin on the surface of peritoneal membrane associated with inflammatory cell infiltration. <b>B, D</b>, <b>F, and H</b> are serial sections of panels <b>A, C, E,</b> and <b>G</b>, respectively. <b>C</b> and <b>D</b> show higher-magnification images of the boxed areas in <b>A</b> and <b>B</b>. Black and blue arrows indicate the same areas in serial sections. <b>A</b>, <b>C</b>, <b>E</b>, and <b>G:</b> HE staining; <b>B</b>, <b>D</b>, <b>F,</b> and <b>H:</b> PTAH staining. Scale bars in <b>A</b> and <b>B</b> = 200 μm. Scale bars in <b>C</b> to <b>H</b> = 100 μm.</p

Differences in general characteristics and pathological findings between the EPS and non-EPS groups matched for PD treatment period, non-diabetes and PD solution (acidic or neutral pH).

<p>Differences in general characteristics and pathological findings between the EPS and non-EPS groups matched for PD treatment period, non-diabetes and PD solution (acidic or neutral pH).</p

General characteristics and pathological findings.

<p>General characteristics and pathological findings.</p

L/V ratio was lower in PD patients with fibrin exudation than in those without fibrin exudation.

<p>A, <b>cohort of</b> <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0154644#pone.0154644.t001" target="_blank">Table 1</a> <b>(n = 83),</b> B: <b>cohort of</b> <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0154644#pone.0154644.t003" target="_blank">Table 3</a> <b>(n = 30).</b></p

Collagen volume fraction (collagen density) in submesothelial compact zone is higher in the EPS development group than in non-EPS development group.

<p><b>A, B:</b> Picrosirius red stain, <b>C, D:</b> Collagen volume fraction (collagen density). <b>A, C:</b> non-EPS development group, <b>B, D:</b> EPS development group. <b>Scale bars = 200 μm.</b></p

Logistic regression analysis of clinical and pathological predictors for EPS.

<p>Logistic regression analysis of clinical and pathological predictors for EPS.</p