Skip Navigation


NDT Advance Access originally published online on October 11, 2006
Nephrology Dialysis Transplantation 2007 22(2):560-567; doi:10.1093/ndt/gfl566
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
22/2/560    most recent
gfl566v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (2)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Hirahara, I.
Right arrow Articles by Kusano, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hirahara, I.
Right arrow Articles by Kusano, E.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

The potential of matrix metalloproteinase-2 as a marker of peritoneal injury, increased solute transport, or progression to encapsulating peritoneal sclerosis during peritoneal dialysis—a multicentre study in Japan

Ichiro Hirahara, Makoto Inoue, Kousuke Okuda, Yasuhiro Ando, Shigeaki Muto and Eiji Kusano

Division of Nephrology, Department of Medicine, Jichi Medical School, 3311-1 Yakushiji, Shimotsuke-city, Tochigi 329-0498, Japan

Correspondence and offprint requests to: Ichiro Hirahara, Division of Nephrology, Department of Medicine, Jichi Medical School, 3311-1 Yakushiji, Shimotsuke-city, Tochigi, 329-0498, Japan. Email: hirahara{at}rpf.jp



   Abstract
Top
 Abstract
Introduction
 Patients and methods
 Results
 Discussion
 Appendix
 Acknowledgements
 References
 
Background. Long-term peritoneal dialysis (PD) leads to peritoneal injury. At worst, peritoneal injury leads to encapsulating peritoneal sclerosis (EPS), which is a serious complication of PD. The mortality rate of EPS is extremely high. To perform PD safely, monitoring of peritoneal injury that leads to EPS is a necessity.

Methods. A total of 444 PD patients with end-stage renal disease at 60 centres in Japan were analysed (sex, 54% males; median age, 56 years; median PD duration, 55 months). Matrix metalloproteinase (MMP)-2 and MMP-9 in the peritoneal effluents were analysed with gelatin zymography or enzyme-linked immunosorbent assay. Cells expressing MMP-2 in the peritoneal tissue were investigated immunohistologically with anti-MMP-2 antibodies. Peritoneal solute transport was assessed with the peritoneal equilibration test (PET).

Results. The MMP-2 levels in peritoneal effluents obtained with the PET were significantly correlated with the D/P Cr ratio (R = 0.69, P < 0.001) and the D/D0 glucose ratio (R = –0.59, P < 0.001). The MMP-2 levels in patients with mild peritoneal injury, moderate peritoneal injury, severe peritoneal injury (EPS) and infectious peritonitis were significantly higher than those in control patients (P < 0.001, P < 0.001, P < 0.01 and P < 0.05, respectively). MMP-2 was produced by myofibroblast-like mesenchymal cells and macrophages in the peritoneum. The peritoneal effluents from patients with infectious peritonitis showed strong MMP-9 signals.

Conclusions. From these results, MMP-2 levels in peritoneal effluents reflect peritoneal solute transport and changes in MMP-2 levels are associated with peritoneal injury that leads to EPS. MMP-2 may be a useful marker of peritoneal injury, increased solute transport or progression to EPS.

Keywords: encapsulating peritoneal sclerosis (EPS); matrix metalloproteinases (MMP); peritoneal dialysis; peritoneal injury



   Introduction
Top
 Abstract
 Introduction
Patients and methods
 Results
 Discussion
 Appendix
 Acknowledgements
 References
 
Peritoneal dialysis (PD) is a common treatment for patients with end-stage renal disease reduced or absent renal function. Long-term PD leads to peritoneal injury with functional decline, such as increased solute transport and ultrafiltration loss. At worst, peritoneal injury leads to encapsulating peritoneal sclerosis (EPS), which is the most serious complication in patients undergoing PD [1–9]. The cause of EPS has not been clarified, but it probably develops through multiple factors. In EPS, evidence of chronic inflammation and ascites is often seen [2–7]. The small intestine appears as a mass encapsulated with thick peritoneum rich in collagenous fibres forming an adhesion, called an abdominal cocoon. It has been reported that administration of steroid drugs is an effective therapeutic method in the early stage of EPS [2–7], but there is no effective treatment in advanced stages, when bowel adhesions have formed, except for surgically dissecting the encapsulated peritoneum using specialized techniques [3–8]. At present, the main diagnostic methods for EPS include abdominal palpation (palpation of the mass) and detecting symptoms of ileus. Some physicians use diagnostic imaging methods, such as radiography, computed tomography and ultrasonography [3–7], but these methods cannot detect early EPS. C-reactive protein (CRP) is often also used as a biochemical marker for inflammation [2–6,10]. However, CRP often does not increase in advanced EPS and cannot be used to differentiate between EPS and infectious peritonitis, because CRP levels increase in infectious peritonitis. As mentioned earlier, steroid therapy is effective in early EPS [2–7], but steroids, which suppress the immune system, may aggravate symptoms when administered to patients with infectious peritonitis. Therefore, a diagnostic method that can differentiate EPS from infectious peritonitis is required. Because of the lack of a reliable early diagnostic method for EPS and the consequent delay in starting appropriate treatment, EPS has a mortality rate of >50% [3–7]. To perform PD safely, it is important to monitor the peritoneal injury that leads to EPS and to diagnose EPS at an early stage.

In cases of sclerosis or fibrosis in various organs, such as artery, lung, liver and kidney, tissue destruction and excessive remodelling occur [11]. In such events, matrix metalloproteinases (MMPs) play important roles. In particular, gelatinases, such as MMP-2 and MMP-9, degrade components of the extracellular matrix (ECM) such as type IV collagen and fibronectin, which comprise the basement membrane, and play important roles in angiogenesis and the migration of cells that promote fibroplasia. Because EPS is accompanied with marked fibrous thickening or sclerosis of the peritoneum, levels of gelatinases are likely increased in this complication. In the present study, we investigated whether gelatinases have a potential as an indicator of the progression to EPS.



   Patients and methods
Top
 Abstract
 Introduction
 Patients and methods
Results
 Discussion
 Appendix
 Acknowledgements
 References
 
Patients
The 444 PD patients (54% males) with end-stage renal disease at 60 centres in Japan were analysed. Patients with appendicitis were excluded. The peritoneal effluents were prepared from April 1999 through July 2005. The patients were divided into five groups as shown in Table 1. The parameters for classification of patients were based on the criteria recommended by the Japanese Sclerosing Encapsulating Peritonitis Study Group [3] and by an International Society for Peritoneal Dialysis Ad Hoc committee [4]. The characteristics of patients are summarized in Table 2. The characteristics of age, sex and aetiology did not differ significantly between groups.


View this table:
[in this window]
[in a new window]

  		Table 1. The definitions of classification of patients

 

View this table:
[in this window]
[in a new window]

  		Table 2. Characteristics of patients with various degrees of peritoneal injury

 
The patients with infectious peritonitis were also compared with the patients without infectious peritonitis. The characteristics of patients are summarized in Table 3. The characteristics of age, PD duration sex and aetiology did not differ significantly between the two groups.


View this table:
[in this window]
[in a new window]

  		Table 3. Characteristics of patients without or with infectious peritonitis

 
The Ethics Committee of Jichi Medical School approved this study protocol, and informed consent was obtained from each patient.

Peritoneal equilibration test (PET)
Peritoneal solute transport was assessed with the PET [12]. A total of 222 patients (sex: 57% males; aetiology of renal failure: 15% diabetic) with a median (interquartile range) age of 56 years (46–65 years) who had undergone PD for a median of 49 months (25–69 months) were analysed with the PET. Intra-abdominal fluid was drained, and the 2 l of PD fluid containing 2.27–2.5% glucose was injected intraperitoneally. The creatinine (Cr) level of peritoneal effluents obtained 4 h after the injection (D) was divided by that of plasma (P) to obtain the D/P Cr ratio. The glucose level of peritoneal effluents obtained 4 h after the injection (D) was divided by that obtained immediately after the injection (D0) to obtain the D/D0 glucose ratio.

Analysis of gelatinases
The gelatinases in peritoneal effluents (0.25 µl) were diluted to 16 times and analysed with gelatin zymography, as described before [13]. MMP-2 or MMP-9 concentration was measured by enzyme-linked immunosorbent assay (ELISA) system (Amersham Bioscience, NJ, USA).

Western blotting analysis
Peritoneal effluents (1 µl) were electrophoresed under non-reducing conditions on 8% polyacrylamide gel and then separated proteins were transferred onto nitrocellulose membranes at room temperature. Membranes were blocked with Block Ace (Snow Brand Co., Hokkaido, Japan) overnight at 7°C and subsequently incubated with a monoclonal antibody against MMP-2 (1:100 dilution, clone No. 42-5D11, Fuji Chemical Industries Ltd., Toyama, Japan) or a monoclonal antibody against MMP-9 (1:50 dilution, clone No. 56-2A4, Fuji Chemical Industries Ltd.) for 2 h at room temperature. After washing with phosphate-buffered saline (PBS) containing 0.05% Tween-20, membranes were incubated with peroxidase-conjugated goat affinity-purified antibody to mouse immunoglobulins (1:1000 dilution; ICN Pharmaceuticals Inc., Cappel Products, Costa Mesa, CA, USA) for 1 h at room temperature. The immunoreactive proteins were visualized with a tetramethyl-benzidene membrane peroxidase substrate (Kirkegaard & Perry Laboratories Inc., Gaithersburg, MD, USA).

Immunohistochemistry
Peritoneal biopsy specimens were obtained from the parietal peritoneum. Peritoneal tissue samples embedded in paraffin were sectioned at a thickness of 2–3 µm. The sections were dewaxed with xylene and ethanol, and endogenous peroxidase activity was blocked with 3% hydrogen peroxide/methanol for 10 min, followed by rinsing with PBS. Sections were then incubated for 4 h at room temperature with a monoclonal antibody against MMP-2 (Fuji Chemical Industries Ltd.) at a dilution of 1:100. Following rinsing with PBS, sections were incubated with peroxidase-conjugated anti-mouse Ig [Histfine Simple-stain PO (MULTI), Nichirei Co., Tokyo, Japan] for 30 min. After washing with PBS, peroxidase activity on the sections was developed with aminoethylcarbazole (Nichirei Co.) as the substrate and then sections were counterstained with Meyer's haematoxylin for 10 s.

Statistical analysis
Data are expressed as medians with the spread from 25th to 75th percentiles. Comparisons between two groups were performed with the Mann–Whitney U-test. Multiple comparisons were performed with the Kruskal–Wallis test, followed with the Steel–Dwass test. Relationships between clinical variables and MMP-2 levels were analysed with Spearman's correlation coefficient test. Statistical analyses were performed with the SAS system for Windows, version 8.2 (SAS Institute Inc., Cary, NC, USA).



   Results
Top
 Abstract
 Introduction
 Patients and methods
 Results
Discussion
 Appendix
 Acknowledgements
 References
 
Analysis of gelatinases in the peritoneal effluents
The gelatinases in peritoneal effluents were analysed with gelatin zymography (Figure 1A). On gelatin zymograms, strong signals of 64 kDa gelatinase were observed in patients with moderate peritoneal injury, but faint signals of 64 kDa gelatinase were detected in control patients and in the patient with infectious peritonitis. The signal of 90 kDa gelatinase was strong in the patient with infectious peritonitis. Western blotting analysis with an anti-MMP-2 or anti-MMP-9 antibody shows positive signals at 64 or 90 kDa, respectively (Figure 1B and C). The 64 and 90 kDa gelatinases were identified as the latent type of MMP-2 (proMMP-2) and the latent type of MMP-9 (proMMP-9), respectively. High molecular weight bands that reacted with the anti-MMP-2 or anti-MMP-9 antibody might be complexes of MMP and other proteins (Figure 1B, lane 2 and Figure 1C, lane 2).


Figure 1
View larger version (28K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 1. Analysis of peritoneal effluents with gelatin zymography. (A) Gelatinases in the peritoneal effluents were analysed with gelatin zymography. Gelatinases were detected as unstained proteolytic bands in gel stained with Coomassie Brilliant Blue. Lane 1: MMP marker (Chemicon International Inc., Temecula, CA, USA). Lane 2: control patient (group 1). Lane 3: patient with mild peritoneal injury (group 2). Lane 4: patient with moderate peritoneal injury (group 3). Lane 5: patient with severe peritoneal injury (EPS) (group 4). Lane 6: patient with infectious peritonitis (group 5). (B) Western blotting analysis of the peritoneal effluents from a control patient (lane 1) and a patient with moderate peritoneal injury (lane 2) using an anti-MMP-2 antibody after electrophoresis under non-reducing conditions. (C) Western blotting analysis of the peritoneal effluents from a control patient (lane 1) and a patient with infectious peritonitis (lane 2) using an anti-MMP-9 antibody after electrophoresis under non-reducing conditions.

 
Relationship between MMP-2 concentration and patient characteristics
Peritoneal solute transport determined with the PET was correlated with the MMP-2 concentrations in peritoneal effluents obtained with the PET (D/P Cr vs MM-2 level; P < 0.001, R = 0.69. D/D0 glucose vs MMP-2 level; P < 0.001, R = –0.59) (Figure 2).


Figure 2
View larger version (10K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 2. Peritoneal solute transport and MMP-2 levels in the peritoneal effluents. Peritoneal solute transport was assessed with the PET. The concentration of MMP-2 in the peritoneal effluents obtained from the PET was also analysed with ELISA. (A) The D/P Cr ratio versus the MMP-2 level. (B) The D/D0 glucose ratio vs the MMP-2 level.

 
No correlations were observed between MMP-2 concentration and age, PD duration, peritonitis episodes, sex and aetiology of renal failure (non-diabetic/diabetic) (Tables 4 and 5).


View this table:
[in this window]
[in a new window]

  		Table 4. Concentration of MMP-2 in peritoneal effluent

 

View this table:
[in this window]
[in a new window]

  		Table 5. Relationship between MMP-2 level in the peritoneal effluent and patient characteristics

 
MMP-2 concentration in various stages of peritoneal injury
The MMP-2 levels in the mild peritoneal injury group (group 2), the moderate peritoneal injury group (group 3) and the severe peritoneal injury group (EPS group) (group 4) were significantly increased. In particular, the MMP-2 level was higher in the moderate peritoneal injury group (group 3) than in any other group. These results are shown in Figure 3. In patients with infectious peritonitis, MMP-9 levels in peritoneal effluents increased markedly with a slight increase in MMP-2 levels. In only four out of 415 patients without infectious peritonitis, slight MMP-9 levels were detected. These results are shown in Figure 4.


Figure 3
View larger version (12K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 3. The MMP-2 levels in the peritoneal effluents from patients with peritoneal injury of various stages. Group 1: control group (n = 311). Group 2: mild peritoneal injury group (n = 78). Group 3: moderate peritoneal injury group (n = 14). Group 4: severe peritoneal injury group (EPS group) (n = 12). Group 5: infectious peritonitis group (n = 29). All data are expressed as medians, with the spread from the 25th to 75th percentile (box) and the spread from the 10th to 90th percentile (bar). Dots show mean values. *P < 0.05, **P < 0.01, ***P < 0.001.

 

Figure 4
View larger version (9K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 4. The levels of gelatinases in the peritoneal effluents from patients without or with infectious peritonitis. The MMP-2 (A) and MMP-9 (B) levels in the effluents are expressed as medians, with the spread from 25th to 75th percentile (box) and the spread from 10th to 90th percentile (bar). Dots show mean values. *P < 0.05, ***P < 0.001.

 
Long-term outcomes in patients with peritoneal injury
Patient outcomes were examined after analysis of MMP-2. In the mild peritoneal injury group (group 2), three patients with MMP-2 concentrations of 623, 1642 and 3541 ng/ml had EPS. In the moderate peritoneal injury group (group 3), five patients with MMP-2 concentrations of 460, 900, 933, 1934 and 2760 ng/ml had EPS. In this group, 36% of patients developed to EPS although 67% of patients had been treated with steroids.

Of the 15 patients with MMP-2 concentration >600 ng/ml except the patients who had presented with EPS when MMP-2 levels were analysed, seven patients (47%) had EPS, though 53% of patients had been treated with steroid. Of the patients with MMP-2 concentration <600 ng/ml, only one patient with 460 ng/ml MMP-2 had EPS.

Production of MMP-2 in the peritoneum
Positive signals for the anti-MMP-2 antibody were detected in myofibroblast-like mesenchymal cells ({alpha}-smooth muscle actin, positive; data not shown) and macrophages in peritoneum specimens obtained from the patient with moderate peritoneal injury (Figure 5).


Figure 5
View larger version (74K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 5. Production of MMP-2 in the parietal peritoneum. The production of MMP-2 in the parietal peritoneum was analysed immunohistologically with an anti-MMP-2 antibody. Myofibroblast-like mesenchymal cells (A) and macrophages (B) show positive signals. Magnification: x200.

 


   Discussion
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
Appendix
 Acknowledgements
 References
 
EPS is the most serious complication of PD, and there is no effective treatment in the advanced stage of EPS except for surgery with specialized techniques. To perform PD safely, it is important to monitor the peritoneal injury that leads to EPS and to diagnose EPS at an early stage.

Peritoneal injury can be inferred on the basis of peritoneal solute transport assessed with the PET. In the present study, peritoneal solute transport correlated with the MMP-2 level in peritoneal effluents, as in a previous study in rats [14]. As peritoneal solute transport correlates with vascular surface area, neovascularization may promote solute transport. Vessel basement membrane degradation by MMP-2 may be an important stage in new blood vessel sprouting, but the mechanism has not been clear yet. In the present study, levels of MMP-2 in effluents were markedly increased in patients with moderate peritoneal injury with ascites, which is present in many cases of early EPS [2]. In addition, EPS developed in half of patients with MMP-2 concentration >600 ng/ml, although half of the patients had been treated with steroids. These results suggest that the MMP-2 might be used as a marker of peritoneal injury, increased solute transport or progression to EPS.

Peritoneal cells, such as macrophages, myofibroblasts, endothelial cells and mesothelial cells are activated by various stimuli, such as peritonitis due to infection with bacteria or fungi, exogenous materials such as particulates, antiseptics, advanced glycosylated end products, glucose degradation products in the PD fluid and the pH of the PD fluid. These activated cells produce various cytokines, growth factors and other mediators that induce peritoneal injury. Macrophages may infiltrate or migrate in the peritoneum while the ECM is being degraded by MMP-2 produced by these cells [15,16]. Activated mesothelial cells may transform to mesenchymal cells (epithelial mesenchymal transition) and infiltrate or migrate in the peritoneum, which is digested by MMP-2 [16,17]. Activated myofibroblasts synthesize ECM proteins or migrate while disassembling the ECM of the peritoneum with MMP-2 or other proteinases [13,15,16]. Excessive ECM proteins, such as collagen, lead to peritoneal fibrosis with peritoneal thickening and promote the production of MMP-2 by myofibroblasts [13]. Fibrin, often deposited in the peritoneum in EPS, also induces the production of MMP-2 by myofibroblasts [13]. In addition, neomicrovascularization may occur while the ECM is being degraded by MMP-2 produced by activated endothelial cells of the microvasculature [16]. As a result of tissue destruction and remodelling with ECM production or degradation by MMP-2, fibrous thickening of the peritoneum may occur and an abdominal cocoon may be formed.

In the present study, MMP-2 was produced by the peritoneal cells as in previous studies in rats [13,15,16]. In addition, there is a possibility that MMP-2 in effluents is transported from the plasma. But in our preliminary study, the measured D/P ratios of MMP-2 were higher than expected when MMP-2 would have been transported from the circulation only by diffusion (data not shown) [18]. In some patients in the moderate peritoneal injury group (group 3), MMP-2 levels in effluents were higher than that in plasmas (data not shown). Levels of MMP-2 in effluents may be strongly affected by MMP-2 produced from the peritoneal cells. The MMP-2 levels in the effluents of patients with severe peritoneal injury (EPS) tended to be lower than those of patients with moderate peritoneal injury. In end-stage EPS, the peritoneum is often acellular [4,9]. The loss of peritoneal cells producing MMP-2 may decrease levels of MMP-2 in the peritoneal effluents.

In the present study, levels of MMP-9, a gelatinase-like MMP-2, were hardly detected in peritoneal effluents of patients without infectious peritonitis. Interestingly, in patients with infectious peritonitis, MMP-9 levels in peritoneal effluents increased markedly with a slight increase in MMP-2 levels. Our data are consistent with most of a previous report [19,20]. These results suggest that peritoneal injury that might lead to EPS can be clearly distinguished from infectious peritonitis by analysing gelatinases in the peritoneal effluents.

This diagnostic method employing peritoneal effluents as samples enables easy sampling, which is noninvasive to patients without pain. An MMP-9 test kit, consisting of an anti-MMP-9 antibody conjugated to a dye in a nitrocellulose membrane, has been developed to diagnose infectious peritonitis [20]. If such test kit for MMP-2 was developed, peritoneal injury could be diagnosed at home.

Our results suggest that MMP-2 may be useful as a marker of peritoneal injury, increased solute transport or progression to EPS that can differentiate from infectious peritonitis. However, it is not concluded that MMP-2 is useful as a diagnostic marker for early EPS, because most patients with moderate peritoneal injury are treated with steroids or discontinue PD to prevent the progression of EPS. Future studies should examine serial changes in MMP-2 levels in relation to the progression of peritoneal injury leading to EPS.



   Appendix
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Appendix
Acknowledgements
 References
 
Collaborators were as follows; Akira Suzuki (Department of Urology, Morioka Yuai Hospital), Akiyasu Tsuchida (Department of Nephrology, Toho Hospital), Eiji Ishikawa (Hemo Dialysis Center, Mie University), Fujio Hamada (Department of Internal Medicine, Saiseikai Sendai Hospital), Harumichi Higashi (Department of Nephrology, St. Mary's Hospital), Hideki Takizawa (Department of Nephrology, Teine Keijinkai Hospital), Hideaki Oda (Director, Oda Clinic), Hidenori Sugawara (The Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University), Hiromi Hidaka (Kidney Internal Medicine, Shiraishi Hospital), Hironobu Kawai (Department of Nephrology, Saiseikai Maebashi Hospital), Hiroshi Miyazaki (Kurume University School of Medicine), Hiroshi Nagae (Department of Urology, Seirei Mikatahara General Hospital), Hiroshi Tanaka (Department of Pediatrics, Hirosaki University School of Medicine), Hiroyuki Tamura (Department of Nephrology, Tokyo Kyosai Hospital), Hisao Mutoh (Department of Internal Medicine, Kanazawa Social Insurance Hospital), Hitoshi Yokoyama (Division of Blood Purification, Kanazawa University Hospital), Ichiro Koni (Division of Rheumatology, Kanazawa University Hospital), Kenji Kasai (Department of Nephrology, Fuji City Central Hospital), Kunio Yoshihara (Mamenoki Clinic), Makoto Nishina (Metabolism, Department of Internal Medicine, Tokai University, School of Medicine), Masaharu Imagawa (Department of Urology, Oita Red Cross Hospital), Masahiro Numano (Kidney Center, Kakegawa City General Hospital), Masao Kim (Director, Kaikou Clinic), Masanobu Horie (Department of Urology, Daiyukaidaiichi Hospital), Mikihiko Fujishima (Director, Yahaba Clinic), Morihiro Kondou (Department of Nephrology, Otowa Hospital), Naomi Yoshimune (Department of Internal Medicine, Kinashi Obayashi Hospital), Noriaki Yorioka (Department of Advanced Nephrology, Graduate School of Biomedical Sciences, Hiroshima University), Noriko Mori (Kidney Center, Shizuoka General Hospital), Noriko Yoshikawa (Department of Nephrology, Tokyo Medical University Hachioji Medical Center), Ryoichi Andou (Department of Nephrology, Musashino Red Cross Hospital), Ryoichi Miyazaki (Department of Internal Medicine, Fujita Memorial Hospital), Satomi Kanemitsu (Department of Pediatrics of Medicine, Kyushu University), Shigeru Marusaki (Department of Internal Medicine, Obihiro Kyokai Hospital), Shigeru Nakai (Department of In Home Medicine, Nagoya University School of Medicine), Sukenari Koyabu (Department of Internal Medicine, Owase General Hospital), Tadashi Yamamoto (Kidney Center, Shirasagi Hospital), Takahide Noguchi (Oogakikita Clinic), Takahiro Kajiwara (Kidney Center, Saitama Social Insurance Hospital), Takahiro Mochizuki (Department of Nephrology, Kameda Medical Center), Takahiro Oonishi (Department of Cardiology, Yamada Red Cross Hospital), Tetsurou Yanase (Dr Yanase Internal Medicine Office), Tohru Mizumasa (Department of Nephrology, Fukuoka Red Cross Hospital), Tohru Nakahata (Section of Pediatrics, Mutsu General Hospital), Toshihiro Sakurai (Department of Nephrology, Oyama Municipal Hospital), Toshio Watanabe (Department of Pediatrics, Gunma University Hospital), Tomoyoshi Kimura (Department of Nephrology, Sendai Social Insurance Hospital), Toyonori Saiki (Department of Nephrology, Saiki Jin Clinic), Tsuguo Mizuno (Department of Internal Medicine, Sanai Hospital), Tsukasa Nagai (Department of Urology, Ibikousei Hospital), Yasuhiro Hirano (Department of Urology, Fujieda Municipal General Hospital), Yasuhiro Okubo (Department of Nephrology, Saiseikai Utsunomiya Hospital), Yoshihiro Matsumoto (Department of Nephrology, Shizuoka City Hospital), Yoshimasa Fujita (Department of Nephrology, Osaka Koseinenkin Hospital), Yoshinori Masunaga (Department of Internal Medicine, Saganoseki Hospital), Yoshitsugu Kaku (Department of Nephrology, Fukuoka Children's Hospital and Medical Center for Infectious Diseases, Kagoshima City Hospital), Yukata Takezawa (Department of Urology, Isesaki Municipal Hospital), Yumiko Ikeda (Department of Nephrology, Yokohama Minami Kyousai Hospital).



   Acknowledgements
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Appendix
 Acknowledgements
References
 
This study was supported by Terumo Co. (Tokyo, Japan). We would like to thank Dr Kiyoshi Sakata Mr Takanobu Ishizuka, and Mr Toyohisa Shiono (Terumo Co.) for their help in statistical analysis, and Dr Ken-ichi Shoufuda (Terumo Co.) for his technical assistance.

Conflict of interest statement. None declared.



   References
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Appendix
 Acknowledgements
 References
 

  1. Gandhi VC, Humayan HM, Ing TS, Daugirdas JT, Geis WP, Hano JE. (1980) Sclerotic thickening of the peritoneal membrane in maintenance peritoneal dialysis patients. Arch Intern Med 140:1201–1203.[Abstract/Free Full Text]
  2. Kasai K, Terawaki H, Otsuka Y, et al. (2000) Clinical evaluation of cases with massive ascites accumulation after discontinuation of CAPD: an attempt to establish the concept of the pre-sclerosing encapsulating peritonitis (pre-SEP) state. Nippon Jinzo Gakkai Shi 42:346–352.[Medline]
  3. Nomoto Y, Kawaguchi Y, Sakai S, et al. (1998) Sclerosing encapsulating peritonitis (SEP) in patients on continuous ambulatory peritoneal dialysis – definition, diagnosis, and treatment recommendations, 1997 update. J Jpn Soc Dial Ther 31:303–311.
  4. Kawaguchi Y, Kawanishi H, Mujais S, Topley N, Oreopoulous DG. (2000) Encapsulating peritoneal sclerosis: definition, etiology, diagnosis, and treatment. Perit Dial Int 20:Suppl 4, S43–S55.[Abstract/Free Full Text]
  5. Kawanishi H. (2005) Encapsulating peritoneal sclerosis. Nephrology 10:249–255.[CrossRef][Medline]
  6. Kawaguchi Y, Saito A, Kawanishi H, et al. (2005) Recommendations on the management of encapsulating peritoneal sclerosis in Japan, 2005: diagnosis, predictive markers, treatment, and preventive measures. Perit Dial Int 25:Suppl 4, S83–S95.[Abstract/Free Full Text]
  7. Nomoto Y, Kawaguchi Y, Kubo H, Hirano H, Sakai S, Kurokawa K. (1996) Sclerosing encapsulating peritonitis in patients undergoing continuous ambulatory peritoneal dialysis: a report of the Japanese Sclerosing Encapsulating Peritonitis Study Group. Am J Kidney Dis 28:420–427.[Web of Science][Medline]
  8. Slingeneyer A, Mion C, Mourad G, Canud B, Faller B, Beraud JJ. (1983) Progressive sclerosing peritonitis: a late and severe complication of maintenance peritoneal dialysis. Trans Am Soc Artif Intern Organs 29:633–638.[Web of Science][Medline]
  9. Dobbie JW. (1992) Pathogenesis of peritoneal fibrosing syndromes (sclerosing peritonitis) in peritoneal dialysis. Perit Dial Int 12:14–27.[Web of Science][Medline]
  10. Hind CR, Thomson SP, Winearls CG, Pepys MB. (1985) Serum C-reactive protein concentration in the management of infection in patients treated by continuous ambulatory peritoneal dialysis. J Clin Pathol 38:459–463.[Abstract/Free Full Text]
  11. Jones CL. (1996) Matrix degradation in renal disease. Nephrology 2:13–23.
  12. Twardowski ZJ, Nolph KD, Khanna R, et al. (1987) Peritoneal equilibration test. Perit Dial Bull 7:138–147.
  13. Hirahara I, Ogawa Y, Kusano E, Asano Y. (2004) Activation of matrix metalloproteinase-2 causes peritoneal injury during peritoneal dialysis in rats. Nephrol Dial Transpl 19:1732–1741.[Abstract/Free Full Text]
  14. Hirahara I, Umeyama K, Urakami K, Kusano E, Masunaga Y, Asano Y. (2001) Serial analysis of matrix metalloproteinase-2 in dialysate of rat sclerosing peritonitis models. Clin Exp Nephrol 5:103–108.[CrossRef]
  15. Hirahara I, Umeyama K, Shofuda K, et al. (2002) Increase of matrix metalloproteinase-2 in dialysate of rat sclerosing encapsulating peritonotis model. Nephrology 7:161–169.[CrossRef]
  16. Hirahara I, Kusano E, Yanagiba S, et al. (2006) Peritoneal injury by methylglyoxal in peritoneal dialysis. Perit Dial Int 26:380–392.[Abstract/Free Full Text]
  17. Yanez-Mo M, Lara-Pezzi E, Selgas R, et al. (2003) Peritoneal dialysis and epithelial-to-mesenchymal transition of mesothelial cells. N Engl J Med 348:403–413.[Abstract/Free Full Text]
  18. Zweers MM, de Waart DR, Smit W, Struijk DG, Krediet RT. (1999) Growth factors VEGF and TGF-beta1 in peritoneal dialysis. J Lab Clin Med 134:103–104.[CrossRef][Web of Science][Medline]
  19. Fukudome K, Fujimoto S, Sato Y, Hisanaga S, Eto T. (2001) Peritonitis increases MMP-9 activity in peritoneal effluent from CAPD patients. Nephron 87:35–41.[CrossRef][Web of Science][Medline]
  20. Ro Y, Hamada C, Io H, Hayashi K, Hirahara I, Tomino Y. (2004) Rapid, simple, and reliable method for the diagnosis of CAPD peritonitis using the new MMP-9 test kit. J Clin Lab Anal 18:224–230.[CrossRef][Web of Science][Medline]
Received for publication: 26.12.05
Accepted in revised form: 29. 8.06


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
U. Sen, W. E. Rodriguez, N. Tyagi, M. Kumar, S. Kundu, and S. C. Tyagi
Ciglitazone, a PPAR{gamma} agonist, ameliorates diabetic nephropathy in part through homocysteine clearance
Am J Physiol Endocrinol Metab, November 1, 2008; 295(5): E1205 - E1212.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
J.-J. Kim, J.-J. Li, K. S. Kim, S.-J. Kwak, D.-S. Jung, D.-R. Ryu, T.-H. Yoo, H. Y. Choi, S. H. Han, H. J. Kim, et al.
High glucose decreases collagenase expression and increases TIMP expression in cultured human peritoneal mesothelial cells
Nephrol. Dial. Transplant., February 1, 2008; 23(2): 534 - 541.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
22/2/560    most recent
gfl566v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (2)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Hirahara, I.
Right arrow Articles by Kusano, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hirahara, I.
Right arrow Articles by Kusano, E.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?