24 research outputs found

    Connective tissue growth factor (CTGF/CCN2) is increased in peritoneal dialysis patients with high peritoneal solute transport rate

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    Mizutani M, Ito Y, Mizuno M, Nishimura H, Suzuki Y, Hattori R, Matsukawa Y, Imai M, Oliver N, Goldschmeding R, Aten J, Krediet RT, Yuzawa Y, Matsuo S. Connective tissue growth factor (CTGF/CCN2) is increased in peritoneal dialysis patients with high peritoneal solute transport rate. Am J Physiol Renal Physiol 298: F721-F733, 2010. First published December 23, 2009; doi:10.1152/ajprenal.00368.2009.-Peritoneal fibrosis (PF) is an important complication of peritoneal dialysis (PD) therapy that often occurs in association with peritoneal high transport rate and ultrafiltration failure (UFF). To study the possible pathogenic role of connective tissue growth factor (CTGF) in the relationship of PF and UFF, dialysate CTGF contents (n = 178) and tissue CTGF expression (n = 61) were investigated by ELISA, real-time PCR, immunohistochemistry, and in situ hybridization. CTGF production with and without TGF-beta(1) stimulation in human peritoneal mesothelial cells (HPMC) from the spent patients' peritoneal dialysate (n = 32) was studied in vitro. The dialysate-to-plasma ratio for creatinine (D/P Cr) was positively correlated to dialysate CTGF concentration and estimated local peritoneal production of CTGF. CTGF mRNA expression was 11.4-fold higher in peritoneal membranes with UFF than in pre-PD renal failure peritoneum and was correlated with thickness of the peritoneum. CTGF protein and mRNA were detected in mesothelium and in fibroblast-like cells. In cultured HPMC, TGF-beta(1)-induced expression of CTGF mRNA was increased at 12 and 24 h and was correlated with D/P Cr. In contrast, bone morphogenic protein-4 mRNA expression was inversely correlated with D/P Cr. Our results suggest that high peritoneal transport state is associated with fibrosis and increased peritoneal CTGF expression and production by mesothelial cells, which can be stimulated by TGF-beta(1). Dialysate CTGF concentration could be a biomarker for both peritoneal fibrosis and membrane function. Functional alteration of mesothelial cells may be involved in progression of peritoneal fibrosis in high transport stat

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

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    <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.

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    <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
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