Immunopathological changes in a uraemic rat model for peritoneal dialysis.

BACKGROUND: Peritoneal dialysis (PD) is a treatment modality for patients with renal failure. Both the uraemic state of these patients and chronic exposure to PD fluid are associated with the development of functional and structural alterations of the peritoneal membrane. In a well-established chronic PD rat model, we compared rats with normal renal function with subtotal nephrectomized rats that developed uraemia. METHODS: Uraemic and control rats received daily 10 ml conventional glucose containing PD fluid, via peritoneal catheters during a 6 week period. Uraemic and control rats receiving no PD fluid served as controls. Parameters relevant for peritoneal defence and serosal healing responses were analyzed. RESULTS: Uraemic animals were characterized by 2-3-fold increased serum urea and creatinine levels, accompanied by a significantly reduced haematocrit. Uraemia (without PD fluid exposure) induced new blood vessels in different peritoneal tissues, accompanied by increased accumulation of advanced glycation end products (AGEs) and elevated levels of angiogenic factors such as vascular endothelial growth factor and monocyte chemoattractant protein-1 (MCP-1) in peritoneal lavage fluid. A much stronger peritoneal response was observed upon PD fluid exposure in non-uraemic rats. This included the induction of angiogenesis and fibrosis in various peritoneal tissues, accumulation of AGEs, immunological activation of the omentum, damage to the mesothelial cell layer, focal formation of granulation tissues and increased MCP-1 and hyaluronan levels in peritoneal lavage fluid. Finally, chronic PD fluid instillation in uraemic rats did not induce an additional peritoneal response compared to PD fluid exposure in non-uraemic rats, except for the degree of AGE accumulation. CONCLUSIONS: Both uraemia and PD fluid exposure result in pathological alterations of the peritoneum. However, uraemia did not induce major additive effects to PD fluid-induced injury. These results substantially contribute to the understanding of the pathobiology of the peritoneum under PD conditions.     

Inhibition of Rho-kinase alleviates peritoneal fibrosis and angiogenesis in a rat model of peritoneal dialysis

Abstract

Background/Aims: The present study investigated whether Rho-kinase inhibition had a therapeutic role on the pathogenesis of peritoneal fibrosis and angiogenesis. Methods: A rat model of peritoneal dialysis was induced by a daily intraperitoneal infusion of 4.25% Dianeal. Those rats were treated with Rho-kinase inhibitor, fasudil. Immunofluorescence, Western blot and RT-PCR were used to detect the expression of TGF-β1, Collagen I, αSMA and VEGF in each group. Microvessel density (MVD) was measured by immunohistochemistry. Rho-kinase activity was determined by western immunoblotting. Results: Rho-kinase was activated in the peritoneum of the PD group, which was inhibited by fasudil. Compared with PD group, the mRNA and protein expressions of TGF-β1, αSMA and Collagen I were significantly downregulated in fasudil treatment groups in a dose-dependent manner, and the expression of VEGF and peritoneal MVD was also significantly downregulated in fasudil treatment groups in a dose-dependent manner. Conclusion: The Rho-kinase was activated in the peritoneum of the peritoneal dialysis rats, and the inhibition of Rho-kinase by fasudil can remarkably decrease peritoneal fibrosis and angiogenesis.     

Ultrastructure of basement membranes of peritoneal capillaries in a chronic peritoneal infusion model in the rat.

BACKGROUND: Long-term peritoneal dialysis with glucose- based dialysis solutions has been associated with diabetiform alterations of peritoneal tissue. A peritoneal infusion model in the rat was developed to study the effect of chronic infusion of a glucose-based dialysis solution and an isotonic non-glucose solution on the ultrastructure of the basement membranes of peritoneal capillaries. The effect of ageing was also studied in an untreated control group. METHODS: A vascular access port (Rat-o-Port) with attached peritoneal catheter was implanted subcutaneously in the neck of nine male Wistar rats. The rats were divided randomly into three groups: the glucose group (n = 3) was infused daily for 20 weeks with 60 ml/kg body weight 3.86% glucose solution. A control group (n = 2) was infused daily for 20 weeks with 60 ml/kg body weight Ringer's lactate. The untreated control group (n = 4) was studied at the onset of the experiment and after 20 weeks. Omental tissue was obtained from each rat at the end of the experimental period for ultrastructural examination. RESULTS: Extensive lamination of basement membranes of omental capillaries was found in the glucose group. This was in contrast to the untreated control group where clear, single basement membranes were seen at the onset of the experiment and after 20 weeks. These latter findings were similar to those in the Ringer's lactate group. CONCLUSIONS: The chronic infusion model in the rat is suitable for the investigation of the effects on the ultrastructure of peritoneal capillaries of chronic exposure to dialysis fluids. The duplications of basement membranes of omental capillaries found in the glucose group show a striking resemblance to those found in long-term peritoneal dialysis patients. This suggests a role for glucose in the development of peritoneal ultrastructural alterations found in long-term peritoneal dialysis.     

Multidirectional approach to study peritoneal dialysis fluid biocompatibility in a chronic peritoneal dialysis model in the rat.

BACKGROUND: Peritoneal dialysis causes the functional and morphological changes in the peritoneum that result from the bioincompatibility of dialysis solutions. We present a model of chronic peritoneal dialysis in the rat that can be used for testing the biocompatibility of dialysis fluids. Methods and Results. Long-term exposure of the peritoneum to dialysis solutions can be performed in rats with implanted peritoneal catheters. Sampling of the dialysate allows the evaluation of intraperitoneal inflammation by examining cell differential and dialysate cytokine levels. Peritoneal permeability can be evaluated at designed time intervals with the peritoneal equilibration test (PET). At the end of dialysis, peritoneal histology is studied with light and electron microscopy. CONCLUSIONS: Such a multidirectional approach is an effective way to test biocompatibility of dialysis solutions.     

Beneficial effects of icodextrin on plasma level of adipocytokines in peritoneal dialysis patients.

OBJECTIVE: Leptin and adiponectin, well-recognized adipocytokines, are reported to contribute to the pathogenesis of atherosclerosis. The aim of this study was to elucidate the effects of icodextrin-based dialysis solution on adipocytokine metabolism. METHODS: In 12 non-diabetic anuric patients on peritoneal dialysis, dialysis solution was changed from glucose-based dialysis solution to icodextrin-based dialysis solution for 6 months. Plasma levels of leptin, adiponectin, lipids (total cholesterol, HDL-cholesterol and triglyceride), insulin, blood glucose and insulin sensitivity index by the homeostasis model assessment (HOMA-IR) were compared before and after the use of the icodextrin solution. RESULTS: Plasma leptin level was decreased from 15.6 (2.5-69.0) to 7.3 (2.9-45.9) ng/ml (P = 0.018) and plasma adiponectin level increased from 11.6 (6.2-19.6) to 17.6 (7.8-33.0) microg/ml (P = 0.002). A reduction in plasma insulin level from 33.1 (13.8-54.1) to 19.1 (5.8-37.3) muU/ml (P = 0.009) and HOMA-IR from 8.22 (3.68-15.09) to 5.15 (1.40-13.78) (P = 0.015) was observed. While plasma total cholesterol level remained similar, HDL-cholesterol level increased, from 36.0 (22-45) to 43.5 (30-69) mg/dl (P = 0.008) and the triglyceride level decreased, from 174.0 (140-250) to 116.5 (81-207) mg/dl (P = 0.012). CONCLUSION: Icodextrin-based dialysis solution improves abnormal adipocytokine metabolism, dyslipidaemia and insulin resistance, which are known to be associated with atherosclerosis. These results suggest that the use of icodextrin-based dialysis solution might be useful in preventing atherosclerosis in PD patients. Long-term effects of icodextrin-based dialysis solution on the atherosclerosis in peritoneal dialysis patients should be tested.     

Effect of renin–angiotensin system inhibitors on prevention of peritoneal fibrosis in peritoneal dialysis patients

Aim: Long‐term peritoneal dialysis (PD) may lead to peritoneal fibrosis and ultrafiltration failure. It had been demonstrated that the renin–angiotensin system (RAS) plays a key role in the regulation of peritoneal function in rats on PD. We investigated the effects of angiotensin‐converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) on long‐term PD patients. Methods: We analyzed data from 66 patients treated with PD therapy at our centre for at least 12 months retrospectively, during which time at least two peritoneal equilibration tests (PET) were performed. Thirty‐eight patients were treated with ACE/angiotensin II (AII) inhibitors (ACE/ARB group); the other 28 received none of the above drugs during the entire follow up (control group). The expression of fibronectin, transforming growth factor‐β1 (TGF‐β1), Aquaporin1 (AQP1) and vascular endothelial growth factor (VEGF) in the overnight effluent were examined by enzyme‐linked immunosorbent assay. Results: The demographic data of the two groups showed no difference during the study. No difference between the groups was found with respect to residual renal function (RRF) at the start for both groups by the end of follow up, decreased in the vast majority of patients from both groups (P = 0.014). After 12 months, a significant difference in ultrafiltration was found between the two groups: in the control group it had decreased, while it had not changed in the ACE/ARB group (P < 0.05). In comparison with the baseline level, expression of fibronectin, TGF‐β1 and VEGF in dialysate effluent were significantly increased except for AQP1 in the control group (P < 0.05), but not in the ACE/ARB group (P > 0.05). Conclusion: The findings suggest that ACE/AII inhibitors appeared to have a slower rate of decline in ultrafiltration and RRF, effectively protect against peritoneal fibrosis in long‐term peritoneal dialysis. Long‐term follow up seems to be required to draw more conclusions.     

Effects of atorvastatin on development of peritoneal fibrosis in rats on peritoneal dialysis

Rational: Peritoneal sclerosis is one of the important complications of long-term peritoneal dialysis (PD). In this study, efficacy of atorvastatin on peritoneal histology and functions in non-uremic rats on PD was tested. Objectives: Twenty-two non-uremic Wistar albino rats were randomized into three groups: Sham (intraperitoneal saline), peritoneal dialysis (PD, intraperitoneal 3.86% dextrose containing PD solution), and treatment (TX, intraperitoneal 3.86% dextrose containing PD solution plus atorvastatin added into drinking water). At the end of a 4-week period, 1 h peritoneal equilibration test was performed. Serum lipids and certain cytokines, mediators, markers, and antioxidant enzyme activities in serum and dialysate were studied. Peritoneal thickness was measured and peritoneal inflammation, fibrosis, and vascular proliferation were scored in histological sections. Main findings: In histological examinations, inflammation, fibrosis, and vascular proliferation were significantly more frequent in PD group than Sham group and it seemed to decrease significantly when atorvastatin was used in conjunction with PD. Additionally, peritoneum was significantly thicker in PD group when compared to that of Sham and TX groups. Serum parameters did not significantly differ between groups. On the other hand, dialysate glutathione reductase (GR) activity and TGF-β were significantly lower in TX group than that of the PD group, whereas dialysate IL-6 level was higher in TX group. Principal conclusions: In our study, atorvastatin use appeared to diminish structural changes in peritoneum. Decreased expression of TGF-β in dialysate may be one of the possible underlying mechanisms.     

Beneficial effects of aminoguanidine on radiotherapy‐induced kidney and testis injury

This experimental study was designed to investigate both protective and therapeutic effects of aminoguanidine (AG), on radiotherapy (RT)‐induced oxidative stress in kidney and testis. Forty rats were divided into five groups equally as follows: (i) control, (ii) RT, (iii) AG, (iv) AG+RT and (v) RT+AG group. Histopathological findings and biochemical evaluations, including tissue malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione (GSH), total oxidant status (TOS), total antioxidant capacity, oxidative stress index (OSI), blood urea nitrogen (BUN), serum creatinine (Cr) and testosterone levels, were determined. MDA, TOS and OSI were significantly higher in RT‐treated groups, whereas SOD, CAT, GPX and GSH were significantly lower in these groups when compared with the control rats in the kidney and testis tissue. AG treatment significantly decreased MDA, TOS and OSI levels and increased SOD, CAT, GPX and GSH levels, when compared to the RT‐treated groups in both kidney and testis tissue. BUN and Cr levels did not change among the groups, whereas testosterone levels were found as reduced in the RT‐treated rats. AG treatment significantly augmented these hazardous effects of RT on testis tissue. According to our results, AG has beneficial effects against RT‐induced kidney and testis injury.     

Effect of PD fluid instillation on the peritonitis-induced influx and bacterial clearing capacity of peritoneal cells.

BACKGROUND: The commonly used peritoneal dialysis fluids contain glucose as the osmotic agent. Heat sterilization leads to the formation of glucose degradation products which contribute, together with glucose, to the formation of advanced glycation end-products (AGEs). AGEs have been shown to be present in the peritoneal cavity. Methods have been developed to minimize the amount of glucose degradation products in peritoneal dialysis fluids. In a rat peritoneal dialysis model, we compare the effect of a commonly used peritoneal dialysis fluid, Gambrosol, with a newly developed peritoneal dialysis fluid, PD-Bio, on the influx and functional capacity of the peritoneal cells after 2 weeks of peritoneal dialysis fluid instillation. METHODS: Three groups of animals were used: rats received daily infusion with 15 ml of either 4% Gambrosol (group 1) or 4% PD-Bio (group 2), and a control group of animals did not receive fluid (group 3). After 2 weeks of PD fluid instillation, all the animals were injected with a 0.5 ml suspension containing 3x10(8) colony-forming units of Staphylococcus aureus. The in vivo bacterial clearing capacity was determined after 15 h. RESULTS: A statistically significant higher leukocyte influx was found in the control group compared with both PD fluid-injected groups. No statistical differences in bacterial clearing were observed among the three groups, although the number of bacteria recovered from the PD-Bio group tended to be lower than that from the Gambrosol group. Moreover, in both PD fluid instillation groups, the bacteria tended to be cleared more slowly compared with the control group. The number of mesothelial cells in the PD fluid groups was significantly greater than in the control group. CONCLUSION: No differences were observed in bacterial clearing capacity, leukocyte influx and mesothelial cell number after a 2 week exposure of the peritoneal cavity to Gambrosol vs PD-Bio.     

Effects of intraperitoneal heparin on peritoneal transport in a chronic animal model of peritoneal dialysis.

BACKGROUND: Heparin has anti-inflammatory effects and is often added to the peritoneal dialysis fluid to prevent fibrin formation. Conjugation of heparin to the surface of biomaterials has been shown to improve its biocompatibility. In this study, we describe for the first time an experimental chronic peritoneal dialysis model with repeated dwell studies in non-uraemic rats and evaluate the effect of addition of heparin to glucose-based peritoneal dialysis fluid on peritoneal fluid and solute transport. METHODS: Wistar male rats, weighing 340+/-15 g, with implanted peritoneal catheters were infused during 1 month, twice per day with 20 ml of Dianeal 1.36%+antibiotics (AB; n = 10) or Dianeal 1.36%+antibiotics+heparin 2500 U/l (HAB; n = 9). After 10 (DS 1) and 30 days (DS 2), a dwell study was performed in rats with free access to drinking water, by infusing 30 ml of Dianeal 3.86%. Dialysate samples were obtained at 0, 2, 30, 60, 120 and 240 min. Blood samples were drawn before and at the end of the dwell. Radiolabelled serum albumin was used as macromolecular volume marker. RESULTS: Peritoneal volumes during DS 1 were significantly greater for the HAB group as compared with the AB group. No differences in ultrafiltration were found during DS 2 for HAB vs AB. However, peritoneal volumes were significantly higher for DS 2 compared with DS 1 in the AB group. The amount of glucose absorbed over time did not differ between the solutions, while fluid absorption tended to be lower in the HAB group. CONCLUSIONS: Heparin may improve peritoneal fluid transport possibly due to better healing and reduced peritoneal inflammation as shown in this novel animal model of chronic peritoneal dialysis with repeated dwell studies.     

Multicenter laparoscopic evaluation of the peritoneum in peritoneal dialysis patients

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.     

Compare the effects of intravenous and intraperitoneal mesenchymal stem cell transplantation on ultrafiltration failure in a rat model of chronic peritoneal dialysis

Aim: The purpose of this study was to compare the possible healing effects of intraperitoneal (IP) and intravenous (IV) mesenchymal stem cell (MSC) transplantation on ultrafiltration failure (UFF) in a chronic rat model of peritoneal dialysis (PD). Methods: Rats were initially divided into two groups. The UFF-group received once-daily IP injections of 20?mL of 3.86% glucose PD solution for six weeks to stimulate the development of UFF, and a control group received no injections. The UFF group was sub-divided into four groups: an UFF-C group, a MSC-IP group, a MSC-IV group and a placebo (P) group. Peritoneal equilibration tests (PETs) and peritoneal biopsies were performed in the control and UFF-C groups. MSCs were administered by IP injection in the MSC-IP group and by IV injection in the MSC-IV group. The P group received IP injection of placebo. PETs and peritoneal biopsies were performed in the MSC-IP, MSC-IV and P groups at the three weeks after receiving MSCs or placebo. Results: When compared with the control group, ultrafiltration capacity significantly decreased, and the submesothelial thickness increased in the UFF-C and P group, but there were no differences between the control and MSC-IP and MSC-IV groups. The rate of glucose transport was high in the UFF-C and P group compared with the control group, and D/P_Cr rates in the UFF-C and P group were lower than in the control group. However, D/D0_glucose was higher and D/P_Cr was lower in the MSC-IP group than in the UFF-C and P groups, but D/D0_glucose rate of MSC-IV group similar to UFF-C and P groups and there was no difference between MSC-IV group and the other groups in terms of D/P_Cr rates. The MSC-IP, MSC-IV and P groups had significantly decreased tumor necrosis factor α concentrations compared with the UFF-C group. MSC-IP group had lower levels of TGF-β1 compared with the P group; MSC-IP group had also lower levels of interleukin-6 compared with UFF-C group. Conclusion: The UFF group had a high permeability UFF. These results showed that IV and IP MSC transplantation exerted positive effects on UFF in a chronic rat model of PD. However, healing effect of small solute transport in MSC-IP group was better than MSC-IV group. IP MSC transplantation may be more effective than IV MSC transplantation for the renewal of the peritoneum in chronic PD patients with UFF.     

Risk factors of severe peritoneal sclerosis in chronic peritoneal dialysis patients

Peritoneal dialysis (PD) offers the healthiest way for starting renal replacement therapy (RRT) in End Stage Renal Disease patients, however exposes long-term PD patients to a dangerous complication named encapsulating peritoneal sclerosis (EPS). In this study, we searched for possible risk factors of EPS. Data were collected from two PD centers covering period 1995–2012 and comprised 464 patients. Control group defined as PD patients stayed on PD >42 month (n?=?122), and case group was 12 confirmed EPS patients. Associations were analyzed using linear regression analysis. Prevalence and incidence of EPS were 2.59% and 8.9% with an incidence of 0.7% patient-years, respectively. The age at start of PD in EPS patients (32.75?±?10.8 year) was significantly lower compared with control group (49.61?±?16.18 year, p?=?.0001). The mean duration of PD in EPS and control group were 2494.4?±?940.9 and 1890.2?±?598.8 days (p?=?.002). Control group had 145 episodes of peritonitis during total duration of 7686 patient months (peritonitis rate of 1/53). This was 1/26 with a total 38 episodes of peritonitis during the total duration of 997 patient months (p?=?.01) for EPS group. In regression analysis, PD duration, age at PD start and duration of Ultrafiltration failure (UFF) were associated with EPS. Longer time being on PD, younger age, and higher UFF duration were the risk factors for EPS development.     

A high peritoneal large pore fluid flux causes hypoalbuminaemia and is a risk factor for death in peritoneal dialysis patients.

BACKGROUND: Hypoalbuminaemia is common in peritoneal dialysis (PD) patients and has an associated high mortality. An excess morbidity and mortality has previously been found in patients with high peritoneal transport. A high peritoneal large pore fluid flux (Jv(L)) results in increased peritoneal loss of protein that possibly contributes to patient morbidity. Alternatively, hypoalbuminaemia and high transport status could be just a marker of capillary pathology associated with atherosclerotic comorbidity. METHODS: Peritoneal dialysis capacity computer modelling of peritoneal transport, based on Rippe's three-pore model, was performed to measure Jv(L) in 155 incident PD patients 2-4 weeks after PD initiation. Patient clinical and biochemical status was determined -6, -3, -1, 1 and 6 months after PD initiation, and every 6 months thereafter. Jv(L) was redetermined in prevalent patients 2 and 4 years after PD initiation. RESULTS: Jv(L) was 0.106+/-0.056 ml/min/1.73 m(2) (median 0.094, interquartile range 0.068-0.128). It was correlated to age*** (*P<0.05; **P<0.01; ***P<0.001) (20-30 years 0.079+/-0.04; 70 years 0.121+/-0.071), but not to gender. No correlation to diabetic or preexisting renal replacement therapy was seen, but patients with atherosclerosis had higher Jv(L) (0.123+/-0.06 vs 0.100+/-0.056*) as had patients with other systemic disease (0.121+/-0.68 vs 0.100+/-0.051*). Jv(L) was positively correlated to area parameter (r = 0.41***), and negatively correlated to plasma albumin (-0.36***). Patients were divided into three equal groups: group 1, Jv(L) <0.075 ml/min/1.73 m(2); group 2, 0.075-0.11; group 3: >0.11. There was no difference between the groups in p-albumin prior to PD. Immediately after PD start, differences between the three groups appeared (1 month p-albumin: (micromol/l) group 1, 548+/-83; group 2, 533+/-86; group 3, 497+/-78**), and persisted for up to 6 years. No significant change in Jv(L) was seen at 2 and 4 years. Patients with significant albuminuria also had hypoalbuminaemia (<1 g/day: 546+/-81 mumol/l; >2 g/day: 503+/-54 micromol/l). Intermittent PD ameliorated the effect of Jv(L) on albumin losses and clearance. Mortality was increased significantly with raised Jv(L), independently of age (2 year mortality: group 1, 10%, group 3, 32%*). There was no overall effect on technique survival, but hypoalbuminaemic group 3 patients had a higher failure rate. CONCLUSION: Jv(L) is related to hypoalbuminaemia and mortality after PD initiation. A high Jv(L) seems to be a marker of preexisting vascular pathology, and to cause hypoalbuminaemia after PD initiation. It is suggested that peritoneal albumin loss can have an identical pathogenic effect as urinary albumin loss, by causing an iatrogenic "nephrotic" syndrome.     

Role of rosiglitazone in lipopolysaccharide-induced peritonitis: A rat peritoneal dialysis model

Aim: The aim of this study was to demonstrate the efficacy of the peroxisome proliferator‐activated receptor (PPAR)‐γ agonist, rosiglitazone, in the amelioration or prevention of inflammation including peritoneal fibrosis secondary to the peritonitis in a peritoneal dialysis (PD) model of non‐uraemic rats. Methods: Thirty male Sprague–Dawley rats were assigned to six groups according to treatment. A 90 min peritoneal equilibrium test, dialysate cellular components, peritoneal thickness and cellularity were assessed on day 21. Additionally, immunohistochemical stains of peritoneal membrane, such as PPAR‐γ, vascular endothelial growth factor (VEGF), transforming growth factor (TGF)‐β1, collagen‐1 and monocyte chemoattractant protein‐1 were performed Results: The dialysate neutrophil count and peritoneal thickness in the high‐dose rosiglitazone group was significantly decreased compared to the lipopolysaccharide (LPS)‐only group. The peritoneal membrane from the LPS‐only group showed marked cellular proliferation in the area of the submesothelial compact zone compared with the PD‐only group, the rosiglitazone‐only group, and the high‐dose rosiglitazone group. The 90 min peritoneal equilibrium test (PET) results showed no statistical difference among the six groups excluding dialysate‐to‐plasma urea ratio. The number of PPAR‐γ expressing cells and the expression of TGF‐β1 were decreased in the high‐dose rosiglitazone group compared to the LPS‐only group. There were no differences in the expression of VEGF and collagen‐1 among the six groups. Interestingly, the number of PPAR‐γ‐positive cells was correlated with expression of VEGF, TGF‐β1, collagen‐1 and monocyte chemoattractant protein‐1 irrespective of the study group. Conclusion: The results of this study showed that rosiglitazone ameliorated peritoneal inflammation induced by LPS and reduced the TGF‐β1 expression in the peritoneal membranes.     

Comparison of infectious complications in peritoneal dialysis patients using either a twin-bag system or automated peritoneal dialysis.

BACKGROUND: Automated peritoneal dialysis (APD) and twin-bag (TB) systems are two major peritoneal dialysis (PD) modalities. Published data comparing the infectious complications of these modalities is limited. Subjects and methods. Ninety-five patients using APD (the APD group) and 117 patients using TB system (the TB group) were recruited. Among them, 35 patients used both modalities. The two groups' clinical characteristics, incidences of infectious complications, and the time intervals to first PD-related infection were compared. RESULTS: Clinical characteristics, incidence of exit-site infection (ESI), and time intervals to first ESI were similar in the TB and APD groups. The incidence of peritonitis in the APD group (1.22 episodes/100 patient-months) was significantly (P < 0.001) lower than that of the TB group (2.28 episodes/100 patient-months). Using the Cox proportional hazard model, APD was found to have a lower risk of peritonitis relative to TB systems, with marginal significance (RR 0.58, P = 0.051). CONCLUSION: APD was found to have a lower peritonitis rate than the TB system. Since reducing the peritonitis rate helps to maintain technical survival during PD, from this viewpoint, APD may be preferred for patients undergoing PD, unless contraindicated.     

Plasma and dialysate IL-6 and VEGF concentrations are associated with high peritoneal solute transport rate.

BACKGROUND: It has been speculated that increased levels of circulating or intraperitoneal pro-inflammatory cytokines such as interleukin 6, and pro-angiogenic vascular endothelial growth factor (VEGF) may contribute to high peritoneal small-solute transport rate (PSTR) in continuous ambulatory peritoneal dialysis (CAPD) patients. In this study we evaluated possible relationships between plasma and dialysate IL-6 and VEGF levels and PSTR. METHODS: Forty CAPD patients (mean age+/-SD of 58+/-14 years) with no apparent inflammation process or disease, who had been on CAPD for 19+/-15 months (range 3-56 months) were included in the study. Peritoneal equilibration test (PET) was used to evaluate PSTR. Patients were divided into two groups: high-average and high transporters (H/A; D/P(creat)>/=0.65) and low-average and low transporters (L/A; D/P(creat)<0.64). Albumin and IgG clearances were used in the evaluation of permeability to larger solutes. Plasma and overnight dialysate levels of IL-6 and VEGF were measured. RESULTS: Plasma IL-6 (7.6 vs 4.3 pg/ml) and VEGF (342 vs 163 pg/ml) as well as dialysate IL-6 (174 vs 80 pg/ml) and VEGF (96 vs 69 pg/ml) levels were significantly higher in the H/A than in the L/A group. The dialysate appearance of IL-6 and VEGF correlated with D/P(creat), as well as with albumin and IgG clearances. Moreover, significant correlations were noted between dialysate IL-6 and dialysate VEGF levels. CONCLUSIONS: The findings of (i) increased plasma and dialysate levels of IL-6 and VEGF in the H/A group compared to the L/A group, (ii) an association between PSTR and both plasma and dialysate IL-6 and VEGF levels, and (iii) a significant correlation between dialysate IL-6 and VEGF concentrations suggest that inflammation, angiogenesis, and peritoneal transport may be interrelated and involved in the pathophysiology of high PSTR in CAPD patients. However, due to the cross-sectional design of this study, the cause and effect relationships between plasma and dialysate IL-6 and VEGF concentrations and high PSRT remain unclear.