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The thin peritoneum covering the peritoneal cavity has been used as a dialysis membrane for peritoneal dialysis (PD) because it is highly vascularized and has a large body surface area. However, it has been reported that peritoneal membranes affected by peritonitis, as well as those exposed to the nonphysiological high glucose levels containing PD dialysate, may undergo histological and functional changes. Patients undergoing PD may experience encapsulating peritoneal sclerosis (EPS), which is a life-threatening serious complication of PD that can significantly impair activities of daily living. The incidence of EPS was 1.4-7.3% of maintenance PD patients in the 1980s. The incidence has improved to 1.0% after a neutral dialysate became the standard PD treatment in Japan. Furthermore, the pathogenesis of EPS is uncertain although its onset may be explained by the "two-hit theory," in which some factors leading to impairment had an additive effect on simple peritoneal sclerosis. The evaluation of histopathological findings has shown the impact of the neutral dialysate on peritoneal deterioration as well as its role in the development of functional changes. In the present report, we discuss the advances in the understanding of peritoneal deterioration based on histological and macroscopic evaluations of the peritoneum of patients undergoing PD. We also discuss the recent treatment for PD patients., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

L-carnitine is an important factor in fatty acid metabolism, and carnitine deficiency is common in dialysis patients. This study evaluated whether L-carnitine supplementation improved muscle spasm, cardiac function, and renal anemia in dialysis patients. Eighty Japanese outpatients (62 hemodialysis (HD) patients and 18 peritoneal dialysis (PD) patients) received oral L-carnitine (600 mg/day) for 12 months; the HD patients further received intravenous L-carnitine injections (1000 mg three times/week) for 12 months, amounting to 24 months of treatment. Muscle spasm incidence was assessed using a questionnaire, and cardiac function was assessed using echocardiography. Baseline free carnitine concentrations were relatively low in patients who underwent dialysis for >4 years. Total carnitine serum concentration, free carnitine, and acylcarnitine significantly increased after oral L-carnitine treatment for 12 months, and after intravenous L-carnitine injection. There was no significant improvement in muscle spasms, although decreased muscle cramping after L-carnitine treatment was reported by 31% of patients who had undergone HD for >4 years. Hemoglobin concentrations increased significantly at 12 and 24 months in the HD group. Therefore, L-carnitine may be effective for reducing muscle cramping and improving hemoglobin levels in dialysis patients, especially those who have been undergoing dialysis for >4 years.

Laparoscopic findings have been used to confirm peritoneal degenerations in peritoneal dialysis (PD) therapy. This study evaluated morphological changes in the peritoneum and their clinical relevance in patients undergoing PD. Laparoscopic findings at the rectovesical peritoneum were evaluated and scored using an imaging system at the time of PD catheter removal in this multicenter study. Angiogenesis evaluated by the vascular score (VS), color changes score (CCS), plaque score (PS), PD duration, history of peritonitis, dialysate/plasma creatinine (D/P Cr) levels, and age at PD termination were statistically analyzed. The VS of patients with PD duration more than 96 months was significantly decreased compared with that of the other patients and was negatively correlated with D/P Cr levels at PD termination. The CCS for patients with PD duration more than 96 months were significantly higher than those for the other patients and positively correlated with D/P Cr levels at PD termination. The PS of patients with recurring peritonitis were significantly higher than those of the other patients. Diminished vascularity and increased color changes in the peritoneum may be predictive of D/P Cr levels with peritoneal degradation. Laparoscopic evaluation of the abdominal cavity can provide detailed information about peritoneal injury., (© 2020 The Authors. Seminars in Dialysis published by Wiley Periodicals, Inc.)

It is well known that a combination therapy with peritoneal dialysis (PD) and hemodialysis (HD) is feasible and may improve clinical status in patients for whom adequate solute and fluid removal is difficult to achieve with PD alone. The objective of the present study was to evaluate whether the therapy is useful in the likelihood of long-term peritoneal membrane and cardiac function. The therapy was 6 days of PD and one session of HD per week. Physical, biochemical, dialysate-to-plasma ratio of creatinine (D/P Cr), arteriovenous fistula (AVF) blood flow, and left ventricular mass index (LVMI) data were prospectively analyzed in 30 patients with measurements performed at 0 and 6 months, and for 21 patients, 12 or 18 months after initiation of the therapy. The levels of hemoglobin (Hb) after therapy were significantly higher than those at the initiation of therapy. The levels of LVMI and human atrial natriuretic peptide (hANP) after therapy were significantly lower than those at the initiation of therapy, whereas AVF blood flow did not change significantly. D/P Cr levels at 6 months after the therapy were significantly lower than those at the initiation of therapy. D/P Cr levels at 12 or 18 months after the therapy were not aggravated. It appears that the therapy improves Hb levels and cardiac function because of adjusting body fluid status. It was indicated that peritoneal function after therapy may be improved. Therefore, combination therapy is useful from the lifestyle viewpoint of patients in the transition period of PD to HD with end-stage kidney disease., (© 2017 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Background: Long-term peritoneal dialysis (PD) causes peritoneal morphological and functional changes, resulting in high transport status featuring increased peritoneal permeability. High transport status is diagnosed by peritoneal equilibration test (PET), a reliable but time-consuming method. We identifed a reliable biomarker in peritoneal effluent to predict high transport status in PD patients., Methods: We collected peritoneal effluent and serum from 33 PD patients and measured common laboratory test parameters. High transport status was determined by PET if the dialysate/plasma ratio of creatinine at 4h dwell (D/P Cr 4h) was ≥0.81., Results: There were significant correlations between D/P Cr 4h and some laboratory parameters in overnight effluent (pancreatic lipase activity, r=0.65, p<0.001; β 2 -microglobulin concentration, r=0.59, p<0.001; IL-6 concentration, r=0.53, p<0.001; and CA125 concentration, r=0.29, p=0.027). In a multivariate logistic regression analysis, the pancreatic lipase activity in overnight effluent was identified as an independent predictor of high transport status even after adjusting for age, PD duration, and glomerular filtration rate [OR=1.43 (95% CI: 1.11-1.83), p=0.005]., Conclusions: The pancreatic lipase activity in overnight effluent is an independent predictor of high transport status in PD patients., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Peritoneal dialysis (PD) catheters often become severely dislocated, which may lead to malfunction. With the aim of preventing this complication, we have developed a simple method of fixing the catheter downwards in the peritoneal cavity (fixation technique), a technique that does not require a laparoscope. Sixteen patients were implanted using the conventional placement technique and 25 patients were implanted using the fixation technique. The location of the catheter tip was classified from grade 1 (downward, normal) to 5 (dislocated). The frequency of dislocation (defined as the extended time and/or decrease in volume when draining the PD solution) was measured for both the fixation technique and conventional placement technique. There was a significant difference in grade between the fixation technique (2.72 ± 1.01) and conventional technique (3.92 ± 1.31). The time until first dislocation was significantly different between the fixation technique (59.3 ± 48.1 days) and conventional technique (8.8 ± 14.6 days). The time until any dislocation was significantly different between the fixation technique (69.2 ± 41.9 days) and conventional technique (12.9 ± 13.7 days). Complications were not significantly different between the fixation technique and conventional technique. The fixation technique appears to be simple, safe, and useful for preventing severe dislocation and for lengthening the time until dislocation in PD patients., (© 2013 Wiley Periodicals, Inc.)

It is well known that bioincompatible peritoneal dialysate plays a central role in the development of peritoneal fibrosis. Peritoneal inflammation continues even after the cessation of peritoneal dialysate stimulation. It is important to establish the definition of persistent inflammation in the peritoneal cavity at the cessation of peritoneal dialysis (PD). The objective of the present study was to determine whether pentraxin 3 (PTX3) in peritoneal effluent (PE) may be a new biomarker in PD patients. Serum, PE, and peritoneal specimens were obtained from 50 patients with end-stage kidney disease at Juntendo University Hospital. Samples of 19 patients were obtained at the initiation of PD and those of 31 patients at the cessation of PD. PTX3, high-sensitivity CRP, and MMP-2 and IL-6 were analyzed. An immunohistological examination using an anti-PTX3 antibody was performed. Expressions of PTX3 were observed in endothelial cells, fibroblasts, and mesothelial cells in the peritoneum. The PTX3 level in PE at the cessation of PD was significantly higher than that at the initiation of PD. Effluent PTX3 levels in patients with a history of peritonitis or a PD duration of more than 8 years were significantly higher than those in patients without peritonitis or patients with a PD duration of <8 years. The PTX3 level was significantly correlated with MMP-2 and IL-6 levels in PE, as well as the thickness of the submesothelial compact zone and the vasculopathy. It appears that PTX3 may be a new biomarker of peritoneal inflammation and progressive fibrosis.

Peritoneal dialysis (PD) is an attractive treatment for patients with end-stage kidney disease (ESKD). However, long-term peritoneal dialysis is associated with development of functional and structural alterations of the peritoneal membrane. Several factors are implicated in the development of peritoneal fibrosis in PD patients. Inflammatory cytokines, which are induced in the peritoneal cavity during peritonitis, may also induce chronic inflammation and fibrosis. Transforming growth factor β1 (TGF-β1) is generally considered to play an important role in peritoneal fibrosis. The objective of this review is to summarize the mechanisms of peritoneal fibrosis using in vitro and in vivo studies, and the current status and future prospects of interventions in the peritoneal fibrosis.

Background: Morphologic changes of the peritoneum such as peritoneal fibrosis and vasculopathy develop during peritoneal dialysis (PD). In 2002, Williams et al. reported microscopic characteristics of peritoneal changes in PD patients. These studies pointed out the importance of establishing a global standard for qualitative and quantitative histological evaluations. The objectives of the present study are (i) to verify the methods for assessing peritoneal thickness and classifying vasculopathy in peritoneal specimens using the assessment of Williams et al. and (ii) to propose a simple assessment that reflects clinical features such as PD duration and peritoneal function., Methods: Parietal peritoneal samples were obtained from 35 patients that included 27 patients with PD and 8 uraemic patients without PD. In all samples, the maximum and average thicknesses of the submesothelial compact (SMC) zone were measured to assess peritoneal interstitial fibrosis using KS400 imaging analysis. Vasculopathy was also assessed by calculation of patency rates of the vascular lumens using the diameter and area, and by measurement of dimensions of vascular wall hyalinization in each vessel specimen., Results: The median values of maximum and average thicknesses of the SMC zone exceeded 200 μm in uraemic patients without PD treatment. There was a significant relationship between the maximum and average thicknesses of the SMC zone (P < 0.0001). Four to 30 vessels were examined in each participant. Various grades of vasculopathy were observed in each specimen. According to the predominant vasculopathy found in each vessel, the prevalence of serious vasculopathy increased with increasing PD duration. Vascular patency calculated from wall thickness was significantly related to that calculated by the area and to the thickness of hyalinization. Average vascular patency assessed from 5 to 10 vessels in each patient having diameters ranging from 10 to 40 μm was related to PD duration and to peritoneal function (D4/P)., Conclusions: A random-points measurement of average SMC thickness provides a descriptive evaluation of the severity of peritoneal fibrosis that minimizes artefacts during processing and avoids human error. In addition, the average patency in post-capillary venules appears to accurately reflect clinical features such as PD duration and peritoneal permeability.

Background: Echocardiography is widely used for the evaluation of cardiac structures and function. The prognostic value of assessment of left cardiac atrium (LA) size in peritoneal dialysis (PD) patients is still unclear. The objective of the present study is to investigate prospectively a longitudinal monitoring of echocardiography parameters after start of PD. We also investigated a correlation study among plasma atrial natriuretic peptide (ANP) level, LA size, and cardiac function undergoing aggressive treatment., Methods: Correlation among plasma ANP, LA size, and cardiac function was prospectively analyzed by Doppler echocardiography in 32 PD patients in Juntendo University Hospital, Tokyo. Measurement of these parameters was performed at 0, 6, 12, 18, and 24 months after start of PD. All patients were treated with an angiotensin type 1 receptor blocker to control blood pressure to less than 140/90 mmHg. Other antihypertensive drugs such as diuretics and/or calcium channel blockers were added if blood pressure rose to over 140/90 mmHg. Hemoglobin and hematocrit levels were targeted at 10.0 g/dL and 30.0% respectively with recombinant human erythropoietin treatment. A diuretic was added or patients decreased their water intake if ANP was more than 43.0 pg/mL or LA diameter (LAD) more than 39 mm, and for other basic markers of volume status. Cardiac function was measured before and after drainage of PD fluid to evaluate the influence of cardiac function., Results: LAD at start of dialysis (36 +/- 4.6 mm) decreased significantly to 33 +/- 3.3 mm (p < 0.05), 33 +/- 3.2 mm (p < 0.05), and 33 +/- 3.6 mm (p < 0.05) after 6, 12, and 24 months, respectively. Ejection fraction after 6 months was significantly increased compared with that at start of dialysis (p < 0.05). Left ventricular mass index (LVMI) after 6, 12, and 24 months was significantly decreased compared with that at start of dialysis (p < 0.05). ANP was 56 +/- 39 pg/mL at start of dialysis and decreased significantly to 33 +/- 19 pg/mL after 24 months (p < 0.05). ANP was significantly correlated with LAD (r = 0.412, p < 0.01), transmitral A wave flow velocity (r = 0.429, p < 0.01), and LVMI (r = 0.426, p < 0.01). Instillation of the dialysis fluid did not affect any parameters except inferior vena cava dimension., Conclusion: This study demonstrates a reduction in LA size and LVMI in PD patients followed over 24 months. Left ventricular structure, contraction, and compliance were well preserved in PD patients undergoing aggressive treatment based on measurements of plasma ANP and LAD.

Background: Proteoglycans (PGs) are dominant extracellular matrices (ECMs) in the peritoneal tissues. Human peritoneal mesothelial cells synthesize small proteoglycans including decorin. Peritonitis and long-term peritoneal dialysis (PD) cause fibrotic changes in the peritoneum that result in ECM remodelling and PG synthesis., Methods: Twenty-five peritoneal tissues from eight patients at initiation of PD, five long-term PD (>6 years) patients with severe peritonitis lasting for almost 1 month, nine patients after long-term PD (>6 years) without peritonitis and three normal subjects were included in the present study. Expressions of decorin, versican, hyaluronan, MMP-2, alfa smooth muscle actin (alphaSMA) and CD68 for macrophages in these specimens were examined by immunohistochemical staining., Results: Although expression of decorin was detected in normal subjects, it was markedly decreased with long-term PD treatment. In long-term PD patients, the expression of versican was observed in their fibrotic-thickened peritoneum. Versican was present in fibrous regions, elastic lamina of the peritoneum, vascular walls and perivascular regions. Hyaluronan was observed in the whole thickened peritoneum, but its distribution differed in part from that of versican. MMP-2 was mainly observed around the blood vessels. Alfa SMA-positive cells, namely 'myofibroblasts' and CD68-positive cells, i.e. macrophages, were observed in the fibrotic-thickened peritoneum of long-term PD patients. Expressions of MMP-2, hyaluronan, SMA and CD68 in the peritoneum were marked in long-term PD patients' samples, which were strongly immunostained by versican, and were especially high in peritonitis patients., Conclusions: It appears that alterations in PGs, including marked induction of versican with peritonitis and disappearance of decorin, are involved in peritoneal remodelling in PD patients. Versican expression was closely related to the appearance of myofibroblasts and macrophages. These observations suggest that the alteration in PG components following PD therapy and severe inflammation contribute to fibrous thickening of the peritoneum.

Peritoneal fibrosis (PF) is invariably observed in patients undergoing long-term peritoneal dialysis (PD). The condition is thought to occur in response to a variety of insults, including bioincompatible dialysates (acidic solution, high glucose, glucose degradation products, or a combination), peritonitis, uremia, and chronic inflammation. Recently, the pathophysiologic mechanisms that contribute to the fibrosing process have been intensively studied. Transforming growth factor-beta has been shown to be a key mediator of PF. Loss of the mesothelial cell layer has been identified in several studies and shown to correlate with submesothelial thickening and vasculopathy. An association has also been identified between increased submesothelial thickness in the peritoneal membrane and increased solute transport, suggesting a relationship between PF and loss of ultrafiltration capacity. Thus, to maintain long-term PD and improve quality of life for patients, it is important to develop interventions for prevention and treatment of PF. Several strategies for peritoneal fibrosis intervention have been reported, including developing biocompatible dialysate, targeting mediators responsible for inflammation and fibrosis, and reconstituting the peritoneum using mesothelial or bone marrow-derived cells. Recent experimental trials in animal models and clinical studies are presented in this review.

Objectives: It is well known that injection of calcitriol (CT) or maxacalcitol (OCT) is very effective in hemodialysis patients with secondary hyperparathyroidism (2HPT). However, it is difficult to use these drugs with peritoneal dialysis (PD) patients with 2HPT because these drugs must be injected two or three times per week. The objective of the present study was to evaluate the stability of physiological activities of CT and OCT in PD bags and to determine the CT or OCT dosage for intraperitoneal (IP) administration., Materials and Methods: We added CT 1.5 microg or OCT 10 microg to Dianeal PD-2 (approximate pH = 5.0, calcium = 0.87 mmol/L; Baxter,Tokyo, Japan), Midpeliq 250 (approximate pH = 7.0, Ca = 1.0 mmol/L;Terumo Corporation, Tokyo, Japan), and Peritoliq 250 (approximate pH = 5.5, Ca = 1.0 mmol/L; Terumo Corp.). Dialysis solutions were collected from the PD bags at 0, 1, 4, 8, 12, 24, 48, and 72 hours after addition of CT and OCT. The activities of CT and OCT in the dialysis effluent were measured by radioimmunoassay. The levels of serum and effluent OCT after a single IP administration of 10 microg OCT were examined in 4 PO patients with advanced 2HPT., Results: Although the levels of CT and OCT in PD bags made of polyvinyl resins decreased by 70% - 75% immediately after injection, levels in PD bags made of polypropylene resins decreased only slightly. The concentration of CT mixed into the acidic solution in glass containers was stable; the decreased concentration of CT in the PD solution might be due to adsorption onto polyvinyl resins. The maximum serum concentration after IP administration of 10 microg OCT was 750 pg/mL after 5 minutes, and remained at 500 pg/mL at 60 minutes. These results show good peritoneal transport of OCT but not rapid disappearance, unlike intravenous administration., Conclusions: If peritoneal administration of vitamin D derivatives is contemplated, it is important to select the composition of PD bag resins, type of vitamin D analog, and time lag to use when deciding the dosage of injectable vitamin D preparations, such as OCT or CT, for IP administration to PD patients. It appears that IP administration in overnight dwells might be useful for PD patients as a complementary vitamin D preparation.

Chronic kidney disease (CKD) is a worldwide public health problem that affects millions of people from all racial and ethnic groups. At end of 2013, over 300,000 Japanese patients had maintenance dialysis therapy (JSDT). In Japan, the major causes of end stage kidney disease (ESKD) are chronic glomerulonephritis (particularly IgA nephropathy), type 2 diabetic nephropathy, and hypertensive nephrosclerosis. Hypertension is a major factor driving the progression of CKD to ESKD. Since many features of the pathogenesis of IgA nephropathy are still obscure, specific treatment is not yet available. However, efforts by investigators around the world have gradually clarified different aspects of the pathogenesis and treatment of IgA nephropathy. Today, around half of all diabetic patients in Japan receive medical treatment. Type 2 diabetic nephropathy is one of the major long-term microvascular complications occurring in nearly 40% of Japanese diabetic patients. The pathogenesis of diabetic nephropathy involves both genetic and environmental factors. However, the candidate genes related to the initiation and progression of the disorder are still obscure in patients with diabetic nephropathy. Regarding environmental factors, the toxicity of persistent hyperglycemia, reactive oxygen species, systemic and/or glomerular hypertension, dyslipidemia and complement are considered to play an important role. The first part of this review covers the pathogenesis of IgA nephropathy and type 2 diabetic nephropathy, and combines the clinicopathological findings in patients with our research on the ddY and KKA-y mouse models (spontaneous animal models for IgA nephropathy and diabetic nephropathy, respectively). In Japan, the major renal replacement therapies (RRT) are peritoneal dialysis (PD) and hemodialysis (HD). The second part of this review focuses on PD and HD. Based on our research findings from patients and as well as from animal models, we discuss strategies for the management of patients on PD and HD. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background The prevention and restoration of peritoneal damage is a critical mission in peritoneal dialysis (PD). Transplantation of mesothelial cells has been suggested to suppress peritoneal injury during PD. Few studies have examined the efficacy and safety of cell transplantation. We evaluated the paracrine effects of mesothelial transplantation during peritoneal repair using immortalized temperature-sensitive mesothelial cells (TSMCs) in chlorhexidine gluconate (CG)-induced peritoneal fibrosis rats. Methods Continuous-infusion pumps containing 8% CG were placed into the abdominal cavity for 21 days. After the removal of the pumps, the TSMCs were injected into the peritoneal cavity at Day 22 (Tx-1 group) or 29 (Tx-2 group). Morphological findings and mRNA expressions of regeneration-related factors were examined at Days 22, 29 and 35. Results Peritoneal thickness was aggravated in the Tx-1 group. Levels of transforming growth factor (TGF)-β, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 mRNA in the Tx-1 group at Day 35 were comparable with those at Day 22. The levels of Snail, B-Raf and ERK-1, markers of epithelial to mesenchymal transition and of the RAS/MAPK pathway in the Tx-1 group, were significantly higher than those in the Tx-2 group. TGF-β and VEGF were produced from the transplanted mesothelial cells and the surrounding cells in the Tx-1 group. Conclusion It appears that the paracrine effect of transplanted mesothelial cells during peritoneal repair is associated with its surrounding condition. It is important to determine the most appropriate time for developing peritoneal repair through mesothelial transplantation. [ABSTRACT FROM AUTHOR]

Backgrounds. Calcium (Ca) and bone metabolism in continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD) patients show a remarkable difference depending on dialysis modalities. The levels of serum Ca and phosphate (P) in HD patients fluctuate contributing to the intermittent and rapid removal of plasma solute unlike in CAPD. Characteristics of plasma solute transport in automated peritoneal dialysis (APD) patients are resembled with that in HD. The purpose of the present study was to examine the difference of transperitoneal Ca removal between APD and CAPD anuric patients. Subjects and Methods. Twenty-three APD anuric patients were enrolled in this study. Biochemical parameters responsible for transperitoneal Ca removal in 24-hour and 4-hour peritoneal effluents were analyzed on CAPD and APD. Results. Transperitoneal Ca removal on APD was smaller compared with that on CAPD. The Ca removal was related to the ultrafiltration during short-time dwell. Decrease of the Ca removal during NPD induced by short-time dialysate dwell caused negative or small Ca removal in APD patients. The levels of intact PTH were increased at the end of PET. Conclusion. It appears that short-time dwell and frequent dialysate exchanging might suppress the transperitoneal Ca removal in anuric APD patients. [ABSTRACT FROM AUTHOR]

Summary: Purpose: It has been reported that acceleration plethysmography (APG) that is a noninvasive and very simple method for the assessment of arterial stiffness. The objectives of the present study were to evaluate usefulness of APG and to compare the data on blood pressure (BP), serum biochemistry, and aortic calcification index (ACI) in chronic kidney disease (CKD) patients. Methods: ACI, systolic BP, diastolic BP, and serum biochemistry values were obtained from 35 hemodialysis (HD group) patients, 15 peritoneal dialysis (PD group) patients and 20 nondialysis patients (CKD Stages 1–5; nondialysis group). After APG, the acceleration plethysmogram aging index (APG-AI) was calculated. Aortic calcification was measured semiquantitatively using computed tomography (CT) images of the abdominal aorta, and then ACI was calculated. Results: Phosphate (PO4) and calcium×phosphate product (Ca×PO4) in the HD or PD groups were significantly higher than those in the nondialysis group. APG-AI and ACI, which are used for evaluation of arteriosclerosis, in HD or PD groups were higher compared with the nondialysis group. APG-AI and ACI increased with aging. APG-AI was significantly correlated with ACI. Conclusion: APG-AI and ACI in the HD and PD groups were more advanced than in the nondialysis group. Aortic calcification in the HD and PD groups was affected by high levels of P and Ca×PO4. There was a significant correlation between APG, a functional evaluation of arteriosclerosis, and ACI, a morphological evaluation. Therefore, it appears that APG might provide valuable information on arteriosclerosis in CKD patients. [Copyright &y& Elsevier]

Background. Establishing a peritoneal mesothelial cell (MC) line in which the native characteristics of primary MCs are constantly maintained in vivo is of great significance for investigating their morphological and functional changes in peritoneal dialysis. We established transgenic (Tg) rats that expressed the temperature-sensitive tsA58 mutant of the simian virus 40 large T-antigen (tsSV40T), which served as a source of immortalized rat cell lines. The cells were immortalized at a permissive temperature of 33°C, although they were differentiated at a non-permissive temperature of 38°C. In this study, we established a novel MC line from tsSV40T Tg rats and evaluated its characteristics. [ABSTRACT FROM PUBLISHER]

Morphologic changes of peritoneum and expression of VEGF in encapsulated peritoneal sclerosis rat models. Background. Simple sclerosis consisted of a thin layer of submesothelial sclerotic tissue in peritoneal dialysis patients. Encapsulated peritoneal sclerosis (EPS) was characterized by thick sclerotic tissue involving vascular alterations in peritoneal dialysis patients. The objective of the present study is to evaluate serial morphologic changes and expressions of angiogenic factors [i.e., vascular endothelial growth factor (VEGF), angiopietin-1 (Ang-1), and angiopoietin-2 (Ang-2)] in EPS rat models. Methods. Twenty-four rats were given a daily intraperitoneal injection of chlorhexidine gluconate and ethanol dissolved in saline (CH). Nine rats were injected with CH and anti-VEGF neutralizing antibody simultaneously. Quantitative blood vessel evaluation was performed by staining for GS1-lectin. The mRNA expression of VEGF, Ang-1, Ang-2, and their receptors was evaluated by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemical staining was performed in peritoneal vessels using anti-VEGF, Ang-1, and Ang-2 antibodies. Hematopoietic stem cells were detected using anti-CD34 antibody. Results. The vessel area, diameter, and length gradually increased until day 21, and then decreased. VEGF and Ang-2 mRNA expressions gradually increased until day 35. In contrast, Ang-1 peaked at day 21 and then decreased significantly. VEGF blockade improved the experimental EPS. In immunohistochemistry, the vessels stained by VEGF and Ang-2 were detected in subfibrous layer. CD34-positive cells were markedly stained at day 21. Conclusion. Neoangiogenesis was observed in a rat model of experimental EPS. VEGF and angiopoietin/Tie system play an important role in the neoangiogenesis in this model. An analysis using this experimental rat model may elucidate the development of EPS in peritoneal dialysis patients. [ABSTRACT FROM AUTHOR]