Complication Of Long-term Peritoneal Dialysis Research Articles

Encapsulating peritoneal sclerosis: Common or rare in peritoneal dialysis?

Encapsulating peritoneal sclerosis (EPS) is a serious and often fatal complication of long-term peritoneal dialysis (PD) with severe malnutrition and poor prognosis. It causes progressive obstruction and encapsulation of the bowel loops. As EPS becomes more prevalent with longer duration of PD, large multicenter prospective studies are needed to establish its incidence and identify risk factors, therapeutic approach, and prognosis.

Encapsulating peritoneal sclerosis: case series from a university center

Background/AimsEncapsulating peritoneal sclerosis (EPS) is an often-fatal complication of long-term peritoneal dialysis (PD). We here report the clinical features of EPS in Korean PD patients from a single university center.MethodsThe data were collected retrospectively from 606 PD patients at Kyungpook National University Hospital, between August 2001 and August 2011. The diagnosis of EPS was based on clinical signs and symptoms, and confirmed by radiological findings.ResultsEight patients (1.3%, four males) were diagnosed with EPS. The mean age of the patients was 48.5 years (range, 33 to 65). The mean duration of PD was 111.8 months (range, 23 to 186). All patients except for one had three or more episodes of peritonitis. Seven patients were diagnosed with EPS after stopping PD, and only one stayed on PD after initial diagnosis and treatment. Total parenteral nutrition and corticosteroids, in addition to tamoxifen therapy, were used to treat most of the patients, and one patient underwent surgery (adhesiolysis). The overall mortality rate was 50%.ConclusionsEPS is a serious, life-threatening complication in patients on long-term PD. To reduce the incidence and mortality rate of EPS, careful monitoring and early diagnosis is needed.

Encapsulating Peritoneal Sclerosis Following Transplantation: Can We Predict Outcome?

Background: Encapsulating peritoneal sclerosis (EPS), a serious complication of long-term peritoneal dialysis (PD) commonly presents as bowel obstruction due to peritoneal sclerosis with characteristic appearances at laparotomy, requiring subsequent enterolysis and peritoneal resection (peritonectomy). It requires multidisciplinary approaches with specialist referral centre input mandatory, due to elective and emergency mortality approaching 15% and 50% respectively. Transplantation's temporal relationship with EPS onset has been studied as immunosuppression and the ‘2nd hit hypothesis’ of peritoneal injury has been recognised as an integral aetiological components of disease development. We aimed to establish mortality and identify potential predictive risk factors for this patient cohort. Methods: A retrospective analysis was completed of EPS cases at a national referral centre over an 11 year period (173 referrals, 133 operated (53 semi-elective; 80 emergencies; Feb 2000-Nov 2011) Post-transplant EPS patients were assessed, with patient and graft survival as primary endpoints. Potential predictive factors for EPS initiation and outcome, including duration from transplant to disease, duration of PD, immunosuppression, pre-operative C reactive protein (CRP) and Albumin were analysed as secondary endpoints. Results: 24 of the operated group had EPS related to transplantation (12M, 12F; median age 49, range 7-69). The overall mortality in this group was 26% (5/24, total mortality 31%, non-transplant mortality 36.8% (p=0.05, Fisher's exact test); elective mortality15%, emergency mortality 56%) All patients had Calcineurin (Tacrolimus) based immunosuppression in the period leading up to EPS diagnosis. 22 had functioning grafts (1 each lost to venous thrombosis and recurrent FSGS) with a median eGFR of 43ml/min (range 3-144) at diagnosis. There were no predictive differences in the surviving and mortality groups for the following parameters (median values): eGFR at time of diagnosis (45±8.1 vs. 35±14.2 ml/min respectively; p=0.08, unpaired t-test); time from transplant to EPS onset (295±57 vs. 344±149.6 days; p=0.37; total group mean time 318±52.5 days); pre-operative CRP (44±28.6 vs. 95±26.5; p=0.9); or length of time on PD (96±14.6 months vs. 120±1.6; p=0.46). There was however a tendency towards prognostic differences for age at surgery (45±3.8 mg/ml vs. 59±4.9; p=0.08) and pre-operative albumin (28±1.4 g/L vs. 22±1.4; p=0.05) EPS surgery does not appear to have an impact on transplant function in surviving patients (median change in GFR 3ml/min; range -14 to 49; p=0.44) Conclusion: EPS can be exacerbated by transplantation and is potentially catastrophic. This is the largest series worldwide of post-transplant EPS and demonstrates improved mortality rates compared to patients with co-existing renal disease. This may reflect a distinct pathophysiological phenomenon but may be due to a reduction in comorbidities associated with successful transplant. There also appear to be no adverse renal function effects for patients undergoing surgery. Reliable models or methods to predict both disease and outcome of treatment are required, but data suggest that younger age and pre-operative nutritional status are important. Successful management should undoubtedly focus on dedicated specialised centres providing treatment to improve outcomes.

Encapsulating Peritoneal Sclerosis After Kidney Transplantation: A Single-Center Experience from 1982 to 2010

Encapsulating peritoneal sclerosis (EPS), a severe complication of long-term peritoneal dialysis (PD), produces a 50% mortality rate. EPS is characterized by progressive and excessive fibrotic thickening of the peritoneum, leading to encapsulation of the bowel and intestinal obstruction which may present after kidney transplantation (KT), a condition known as posttransplantation EPS. In this study we reviewed 1,500 KT performed in our center from 1982 to 2010, seeking to evaluate the influence of EPS incidence on kidney recipient and graft survival. We detected severe posttransplantation EPS among 16 adult single-kidney cadaveric-donor recipients. The EPS patients (age, 46.68 ± 10.62 years; female/male 5/11) were initially compared with a strictly selected group (n = 48) of non-EPS patients (age, 46.35 ± 10.26 years; female/male, 18/30). Peritoneal dialysis (PD) duration was significantly higher in the EPS group (47.75 ± 9.77 vs. 25.87 ± 10.43 months; P < .0001). This relationship was not only evident on univariate analysis, but also in a multivariate logistic regression model that entered previously selected variables: age (P = .518), sex (P = .796), serum creatinine (P = .441), estimated glomerular filtration rate (P = .566), and diagnostic category (P = .804). Diagnostic plots confirmed the reliability of the logistic regression models. In conclusion, EPS which negatively influences the outcome and quality of life of kidney recipients, was related to PD duration before to KT.

Post-transplantation encapsulating peritoneal sclerosis in a pediatric patient

Encapsulating peritoneal sclerosis (EPS) is a serious complication of long-term peritoneal dialysis (PD), but only a few cases have been described in the pediatric patient population. There is no established medical treatment, and surgery has been reported with variable success. The number of reports of EPS being successfully treated with tamoxifen, based on its anti-fibrotic effects, are increasing. The role of sirolimus, an mTOR inhibitor with immunomodulatory and anti-proliferative properties, has been less well-defined. A 17-year-old kidney transplant recipient, with a previous cumulative time on PD of 8 years and 3 months, developed severe bowel obstruction 8 months after undergoing a second kidney graft. Her immunosuppressive regimen consisted of tacrolimus, mycophenolate mofetil, and prednisolone. The patient underwent laparotomy, which revealed multiple thick leathery adhesions with an encapsulated small bowel. Enterolysis was performed, and total parenteral nutrition was commenced after surgery to provide an adequate food intake. Treatment with tamoxifen was initiated, but the patient developed significant liver toxicity 2 weeks later, and the drug was withdrawn. The immunosuppressive regimen was changed to an increased dose of prednisolone, and tacrolimus was replaced with sirolimos. At 20 months of follow-up, the patient remains symptom-free, with a functioning kidney transplant. Although EPS is a very rare condition in the pediatric population, it should be considered when a child or adolescent with a long-term history of PD presents with nonspecific gastrointestinal symptoms or with signs of bowel obstruction. There is an urgent need for alternative immunosuppressive protocols. The use of sirolimus in this group of patients remains controversial.

Activation of p38 Mitogen-Activated Protein Kinase Promotes Peritoneal Fibrosis by Regulating Fibrocytes

Peritoneal fibrosis is a serious complication of long-term peritoneal dialysis, and yet the precise pathogenic mechanisms of peritoneal fibrosis remain unknown. Fibrocytes participate in tissue fibrosis and express chemokine receptors that are necessary for migration. The p38 mitogen-activated protein kinase (MAPK) pathway regulates the production of chemokines and has been demonstrated to contribute to the pathogenesis of various fibrotic conditions. Accordingly, we used an experimental mouse model of peritoneal fibrosis to examine the dependency of fibrocytes on p38MAPK signaling. Peritoneal fibrosis was induced in mice by the injection of 0.1% chlorhexidine gluconate (CG) into the abdominal cavity. Mice were treated with FR167653, a specific inhibitor of p38MAPK, and immunohistochemical studies were performed to detect fibrocytes and cells positive for phosphorylated p38MAPK. The involvement of p38MAPK in the activation of fibrocytes also was also investigated in vitro. Fibrocytes infiltrated peritoneum in response to CG, and that response was accompanied by progressive peritoneal fibrosis. The phosphorylation of p38MAPK, as defined by CD45+ spindle-shaped cells, was detected both in peritoneal mesothelial cells and in fibrocytes. The level of peritoneal expression of CCL2, a chemoattractant for fibrocytes, was upregulated by CG injection, and treatment with FR167653 reduced the number of cells positive for phosphorylated p38MAPK, the peritoneal expression of CCL2, and the extent of peritoneal fibrosis. Pretreatment with FR167653 inhibited the expression of procollagen type I α1 induced by transforming growth factor-β1. Our results suggest that p38MAPK signaling contributes to peritoneal fibrosis by regulating fibrocyte function.

MicroRNAs in peritoneal dialysis effluent are promising biomarkers for peritoneal fibrosis in peritoneal dialysis patients

Peritoneal fibrosis is a common complication of long-term peritoneal dialysis, and contributes to encapsulating peritoneal sclerosis and eventually peritoneal ultrafiltration failure, which restricts the wide application of peritoneal dialysis. Therefore, the prevention and treatment of peritoneal fibrosis is important to maintain peritoneal membrane integrity and prolong peritoneal dialysis treatment. Unfortunately, neither specific biomarkers nor effective therapies are available for peritoneal fibrosis in the clinic up to now. Emerging evidence suggests that extracellular microRNAs in body fluids are promising biomarkers for the diagnosis of diseases. microRNAs were reported to be involved in multiple fibrotic diseases and the serum levels of specific microRNAs were correlated with the degree of fibrosis. Moreover, extracellular microRNAs were found in peritoneal fluids and ascites. Based on these findings, here we present our hypothesis that extracellular microRNAs associated with peritoneal epithelial-to-mesenchymal transition and fibrosis could potentially be detected in peritoneal dialysis effluent, and serve as novel biomarkers for early assessment and diagnosis of peritoneal fibrosis.

Encapsulating peritoneal sclerosis: the state of affairs

Encapsulating peritoneal sclerosis (EPS) is a severe complication of long-term peritoneal dialysis (PD) with a 50% mortality rate. EPS is characterized by progressive and excessive fibrotic thickening of the peritoneum, leading to encapsulation of the bowels and intestinal obstruction. At present, EPS cannot be detected with certainty during its early stages; however, a progressive loss of ultrafiltration capacity often precedes its development. Studies that attempted to elucidate the pathogenesis of EPS have shown that the duration of exposure to PD fluids is the most important risk factor for EPS, and that young age and possibly the effects of peritonitis are additional contributory factors. The pathophysiology of EPS is probably best described as a multiple-hit process with a central role for transforming growth factor β. A form of EPS that develops shortly after kidney transplantation has also been recognized as a distinct clinical entity, and may be a common form of EPS in countries with a high transplantation rate. Criteria have been developed to identify EPS by abdominal CT scan at the symptomatic stage, but further clinical research is needed to identify early EPS in asymptomatic patients, to clarify additional risk factors for EPS and to define optimal treatment strategies.

Beneficial Effects of Enalapril on Chlorhexidine Digluconate-Induced Liver Peritoneal Fibrosis in Rats

Peritoneal fibrosis (PF) is a recognized complication of long-term peritoneal dialysis (PD) and can lead to ultrafiltration failure. The present study was designed to investigate the protective effects of enalapril on chlorhexidine digluconate-induced liver PF by decreasing transforming growth factor-β1 (TGF-β1) production in rats. PF was induced in Sprague-Dawley rats by daily administration of 0.5 ml 0.1% chlorhexidine digluconate in normal saline via PD tube for one week. Rats received daily intravenous injections of low dose enalapril (1 mg/kg), or high dose enalapril (2.5 mg/kg), for one week. After 7 days, conventional 4.25% Dianeal (30 ml) was administered via a PD catheter with a dwell time of 4 h and assessment of peritoneal function. At the end of dialysis, the rats were sacrificed and liver peritoneum was harvested for microscopic examination and immunohistochemistry. There was no significant difference in mean arterial pressure and heart rate between groups. After 4 h of PD, the D₄/P₄(urea) level was reduced, the D₄/D₀ glucose level, serum and the dialysate TGF-β1 level was increased, the liver peritoneum was markedly thicker, and the expression of TGF-β1, alpha-smooth muscle actin (α-SMA), fibronectin, collagen and vascular endothelial growth factor (VEGF) were elevated in the PF group compared with the vehicle group. High dose of enalapril decreased the serum and dialysate TGF-β1 levels, decreased the thickness of the liver peritoneum, and decreased the expression of TGF-β1, α-SMA, fibronectin, collagen and VEGF-positive cells in the liver peritoneum. Low dose of enalapril did not protect against chlorhexidine digluconate-induced PF in the rat. Enalapril protected against chlorhexidine digluconate-induced PF in rats by decreasing TGF-β1 production.

Imaging in encapsulating peritoneal sclerosis

Encapsulating peritoneal sclerosis (EPS) is a rare but very severe complication of long-term peritoneal dialysis (PD). Since the first reports on this disease in the eighties, several imaging techniques have been used for its diagnosis. Because of the rarity of this condition, uniformity in modality and protocols for abdominal imaging for diagnosis has been lacking overtime. Nowadays, computed tomography (CT) is most often used. In this review, we provide an overview of all imaging modalities that have been used overtime to diagnose EPS as a late complication of PD. Imaging features characteristic for EPS and advantages as well as shortcomings of all modalities are discussed. We believe that when EPS is suspected, CT with contrast enhancement should be the modality of first choice in clinical practice.

Atrial natriuretic peptide ameliorates peritoneal fibrosis in rat peritonitis model

Atrial natriuretic peptide (ANP) was recently reported to ameliorate fibrosis in the heart and experimental renal diseases and vascular thickening after balloon injury. Peritoneal fibrosis is an important complication of long-term peritoneal dialysis, and peritonitis is a factor in its onset. In the present study, we investigated the effects of ANP in a rat peritonitis-induced peritoneal fibrosis model. As pretreatment, an osmotic pump containing vehicle (saline) or ANP (0.15 or 0.3 μg/min) was inserted through the carotid vein in male Sprague-Dawley rats. ANP or saline was continuously infused using the osmotic pump. Three days after administration of ANP or saline, rats underwent peritoneal scraping in a blind manner and were sacrificed on Day 14. The effects of ANP were evaluated based on peritoneal thickness, immunohistochemistry and real-time polymerase chain reaction. In each experiment, we evaluated messenger RNA (mRNA) expression of the ANP receptor natriuretic peptide receptor A (NPR-A) in the peritoneum after scraping. The effects of ANP were also studied in cultured peritoneal fibroblasts and mesothelial cells. We observed a significant increase in NPR-A mRNA in the peritoneum. Peritoneal thickness increased with time and peaked on Day 14, but ANP significantly reduced peritoneal thickness. Parameters such as number of macrophages and CD-31-positive vessels and expression of type III collagen/transforming growth factor-β/plasminogen activator inhibitor-1 (PAI-1)/connective tissue growth factor (CTGF) were significantly suppressed by ANP. In cultured peritoneal fibroblasts and mesothelial cells, ANP suppressed angiotensin II-induced upregulation of CTGF and PAI-1. Our results suggest that ANP is useful in preventing inflammation-induced peritoneal fibrosis.

Incidence of Encapsulating Peritoneal Sclerosis: A Single-Center Experience with Long-Term Peritoneal Dialysis in the United States

Encapsulating peritoneal sclerosis (EPS) is a serious complication of long-term peritoneal dialysis (PD). The reported incidence varies between 0.5% and 4.4% and increases with length of time on PD. Very few data are available on the epidemiology of EPS in the United States. The aim of the present study was assess the incidence of EPS in a single center in New Haven, Connecticut. In a retrospective analysis of all patients maintained on PD for 5 or more years, clinical symptoms were documented, abdominal computed tomography (CT) findings were reviewed, and surgical and pathology findings were noted. Patients were tracked whether they remained on PD, transferred to hemodialysis (HD), underwent transplantation, or died. Among the 76 patients that met the inclusion criteria (mean dialysis duration: 81.5 ± 22 months), 14 (18%) developed clinical symptoms (persisting for 3 or more months) suggestive of EPS. Abdominal CT imaging was done in 38 patients; 25 had radiologic features consistent with EPS. At laparotomy, 6 of 7 patients had gross findings consistent with EPS. Eleven patients met the 2000 criteria of the International Society for Peritoneal Dialysis for a diagnosis of EPS; they had clinical features, plus either radiologic or histopathologic confirmation. In 3 patients with clinical symptoms, the radiologic or surgical findings did not support a diagnosis of EPS. Of the 11 patients meeting the EPS criteria, 1 remains on PD and is doing well, 2 were transferred to HD and are doing well, 2 died as a result of EPS complications, and 6 died of other causes. The present study suggests that, in patients maintained on PD for 5 or more years at our center, the incidence of EPS is 14%. Those findings suggest that EPS may be underrecognized in the United States and that a high index of suspicion is warranted in patients maintained on PD for 5 or more years.

Tanshinone IIA Attenuates Peritoneal Fibrosis through Inhibition of Fibrogenic Growth Factors Expression in Peritoneum in a Peritoneal Dialysis Rat Model

Background: Peritoneal fibrosis is a common complication of long-term peritoneal dialysis (PD) and is the main cause of dialysis inadequacy and PD withdrawal. It has been reported that Tanshinone IIA can ameliorate fibrosis in various tissues. In this report, we investigate the effects of Tanshinone IIA on peritoneal fibrosis in an animal model. Methods: Forty rats were randomly divided into four groups (n = 10 per group) that received daily intraperitoneal injection of saline, 4.25% glucose-based peritoneal dialysis fluid (PDF), or PDF along with 50 or 100 mg/L Tanshinone IIA. Eight weeks later, the rats were sacrificed and peritoneal tissue samples were collected for analysis. The expression of transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) in parietal peritoneum was examined by immunohistochemistry. The mRNA and protein expression of TGF-β1 and CTGF in omentum was examined by reverse transcription polymerase chain reaction or Western blot. Results: Tanshinone IIA significantly suppressed submesothelial compact zone thickening and matrix accumulation induced by 4.25% glucose-based PDF. Tanshinone IIA also reduced TGF-β1 and CTGF expression in parietal peritoneum as well as in omentum in a dose-dependent manner. Conclusion: Tanshinone IIA prevented the progression of peritoneal fibrosis in this rat model. Tanshinone IIA may be a novel therapy for peritoneal fibrosis in patients undergoing long-term PD.

Valsartan decreases TGF-β1 production and protects against chlorhexidine digluconate-induced liver peritoneal fibrosis in rats

Peritoneal fibrosis (PF) is a recognized complication of long-term peritoneal dialysis (PD) and can lead to ultrafiltration failure. The present study was designed to investigate the protective effects of valsartan on chlorhexidine digluconate-induced PF by decreasing TGF-β1 production in rats. PF was induced in Sprague–Dawley rats by daily administration of 0.5 ml 0.1% chlorhexidine digluconate in normal saline via peritoneal dialysis (PD) tube for 1 week. Rats received daily intravenous injections of low dose valsartan (1 mg/kg) or high dose valsartan (3 mg/kg) for 1 week. After 7 days, conventional 4.25% Dianeal (30 ml) was administered via a PD catheter with a dwell time of 4 h and assessed of peritoneal function. At the end of dialysis, rats were sacrificed and the liver peritoneum was harvested for microscopically and immunohistochemistry. There was no significant difference in mean arterial pressure and heart rate between groups. After 4 h of PD, the D 4/P 4Urea level was reduced, the D 4/D 0 glucose level, serum and dialysate transforming growth factor-β1 (TGF-β1) level was increased, the liver peritoneum was markedly thicker, and the expression of TGF-β1, alpha-smooth muscle actin (α-SMA), fibronectin, collagen, and vascular endothelial growth factor (VEGF) were elevated in the PF group compared with the vehicle group. High dose of valsartan decreased the serum and dialysate TGF-β1 level, decreased the thickness of the liver peritoneum, and decreased the expression of TGF-β1, α-SMA, fibronectin, collagen, and VEGF-positive cells in liver peritoneum. The low dose of valsartan did not protect against chlorhexidine digluconate-induced PF in rat. Valsartan protected against chlorhexidine digluconate-induced PF in rats by decreasing TGF-β1 production.

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.

Podoplanin-positive cells are a hallmark of encapsulating peritoneal sclerosis

Encapsulating peritoneal sclerosis (EPS) and simple peritoneal sclerosis are important complications of long-term peritoneal dialysis (PD). Podoplanin is expressed by mesothelial cells and lymphatic vessels, which are involved in inflammatory reactions in the peritoneal cavity. We studied 69 peritoneal biopsies from patients on PD (n = 16), patients with EPS (n = 18) and control biopsies taken at the time of hernia repair (n = 15) or appendectomy (n = 20). Immunohistochemistry was performed to localize podoplanin. Additionally, markers of endothelial cells, mesothelial cells, myofibroblasts (smooth muscle actin), proliferating cells, and double labelling for smooth muscle actin/podoplanin were used on selected biopsies. Podoplanin was present on the endothelium of lymphatic vessels in the submesothelial fibrous tissue and on mesothelial cells. In patients on PD and in biopsies with appendicitis, the mesothelial cells demonstrated a cuboidal appearance and circumferential podoplanin staining, with gaps between the cells. The number of lymphatic vessels was variable, but prominent at sites of fibrosis. In patients with EPS, a diffuse infiltration of podoplanin-positive cells with a fibroblastic appearance was present in 15 out of 18 biopsies. This pattern was focally present in 3 out of 16 on PD and none in the 35 controls. The podoplanin-positive cells did not express the endothelial marker or the mesothelial marker (calretinin). EPS is characterized by a population of podoplanin and smooth muscle actin double-positive cells. Podoplanin might be a suitable morphological marker supporting the diagnosis and might be involved in the pathogenesis of EPS.

The Role of Peritoneal Lavage and the Prognostic Significance of Mesothelial Cell Area in Preventing Encapsulating Peritoneal Sclerosis

Severe peritoneal injury and encapsulating peritoneal sclerosis (EPS) as complications of long-term peritoneal dialysis (PD) are issues of concern. The usefulness of peritoneal lavage after withdrawal of PD and the risk factors for EPS have not been addressed until now. Little is known about mesothelial cell area (MCA) in the effluent as a marker of peritoneal injury. In the present study, we investigated the clinical significance of peritoneal lavage after PD withdrawal and tried to clarify the risk factors related to MCA, with the aim of preventing EPS. We also developed an algorithm for the clinical management of long-term PD patients. We assigned 247 PD patients to one of two cohorts after PD withdrawal: a non-lavage group (73 patients) and a lavage group (174 patients). To clarify the risk factors, we studied these potential predictors: PD duration, dialysate-to-plasma ratio of creatinine (D/P Cr) at the time of PD withdrawal, frequency of peritoneal lavage, type of PD or lavage solution, MCA at the time of PD withdrawal ("PD area"), and MCA at the time of peritoneal lavage withdrawal or censoring ("LA area"). Recurrent intestinal obstruction was defined as the main manifestation of EPS. Diagnostic performance and cut-off values were then calculated for the selected risk factors. The overall incidence of EPS was significantly lower in the lavage group, at 6.9% (5.2% during lavage and 2.5% after lavage), than in the non-lavage group, at 15.1%. The risk factors and cut-off values were PD area (350 µm(2)) and PD duration (78 months) for the non-lavage group; and PD area (350 µm(2)) and LA area (320 µm(2)) for the lavage group. Patients with a PD duration of 78 months or more and a PD area of 350 µm(2) or more were defined as high-risk patients in the non-lavage group (risk ratio: 11.14), and patients with a PD area of 350 µm(2) or more and an LA area of 320 µm(2) or more were defined as high-risk patients in the lavage group (risk ratio: 10.43). Peritoneal lavage is effective in reducing the incidence of EPS after PD withdrawal. The PD duration and MCA are significant risk factors, and these markers are useful for classifying patients into low- and high-risk groups for the development of EPS.

Aliskiren ameliorates chlorhexidine digluconate‐induced peritoneal fibrosis in rats

Peritoneal fibrosis (PF) is a recognized complication of long-term peritoneal dialysis (PD) and can lead to ultrafiltration failure. The present study was designed to investigate the protective effects of aliskiren on chlorhexidine digluconate-induced PF in rats. The PF was induced in Sprague-Dawley rats by daily administration of 0.5 mL 0.1% chlorhexidine digluconate in normal saline via PD tube for 1 week. Rats received daily intravenous injections of low-dose aliskiren (1 mg kg(-1)) or high-dose aliskiren (10 mg kg(-1)) for 1 week. After 7 days, conventional 4.25% Dianeal (30 mL) was administered via a PD catheter with a dwell time of 4 h and assessed of peritoneal function. At the end of dialysis, rats were sacrificed and the liver peritoneum was harvested for microscopically and immunohistochemistry. There was no significant difference in mean arterial pressure and heart rate between groups. After 4 h of PD, the D(4)/P(4) urea level was reduced, the D(4)/D(0) glucose level, serum and dialysate transforming growth factor-beta1 (TGF-beta1) level was increased, the liver peritoneum was markedly thicker, and the expression of TGF-beta1, alpha-smooth muscle actin (alpha-SMA), fibronectin, collagen, and vascular endothelial growth factor (VEGF) were elevated in the PS group compared with the vehicle group. Aliskiren decreased the serum and dialysate TGF-beta1 level, decreased the thickness of the liver peritoneum, and decreased the expression of TGF-beta1, alpha-SMA, fibronectin, collagen, and VEGF-positive cells in liver peritoneum. Moreover, high-dose aliskiren had better protective effects against PF than low dose in rats. Aliskiren protected against chlorhexidine digluconate-induced PF in rats by decreasing TGF-beta1 production.

Early Diagnostic Markers for Encapsulating Peritoneal Sclerosis: A Case-Control Study

Encapsulating peritoneal sclerosis (EPS) is a severe complication of long-term peritoneal dialysis (PD). The aim of this study was to investigate whether dialysate levels of cancer antigen-125 (CA125), K(+), interleukin (IL)-6, and vascular endothelial growth factor (VEGF) are early diagnostic markers of EPS. Therefore, we analyzed the time courses of the above described dialysate markers in EPS patients and controls. Dialysate and serum samples of 11 EPS patients and 31 control patients, all treated with PD for at least 57 months, were longitudinally collected during standard peritoneal permeability analyses. CA125 and IL-6 were measured in dialysate only, K(+) and VEGF were measured in both dialysate and serum. CA125 and IL-6 are expressed as appearance rates (AR). The linear mixed model was used to analyze the time courses. Sensitivity and specificity were calculated based on the results of the last 2 time points. No differences in the time courses of the different markers were present between the groups. For K(+) and VEGF attributed to local production, no differences between the groups were found. However, AR-CA125 was lower during the last 3 years prior to EPS (p < 0.05) and AR-IL-6 tended to be higher 2 years prior to EPS (p = 0.09). The combination of AR-CA125 < 33 U/min and AR-IL-6 > 350 pg/min had a sensitivity of 70% and a specificity of 89% for the development of EPS. Compared to controls, AR-CA125 showed lower values and AR-IL-6 tended to be higher during the last years prior to the diagnosis of EPS. The sensitivity and specificity of the combination of CA125 and IL-6 indicate their potential use for an early diagnosis of EPS.

Long-term peritoneal dialysis and encapsulating peritoneal sclerosis in children

Encapsulating peritoneal sclerosis (EPS) is the most serious complication of long-term peritoneal dialysis (PD), with a mortality rate that exceeds 30%. There have been many reports of the incidence of EPS being strongly correlated to the duration of PD. Patients on PD for longer than 5 years, and especially those receiving this treatment for more than 8 years, should undergo careful and repeated surveillance for risk factors associated with the development of EPS. The development of ultrafiltration failure, a high dialysate/plasma creatinine ratio, as determined by the peritoneal equilibration test, peritoneal calcification, a persistently elevated C-reactive protein level, and severe peritonitis in patients on PD for longer than 8 years are signals that should prompt the clinician to consider terminating PD as a possible means of preventing the development of EPS. The impact of the newer, biocompatible PD solutions on the incidence of EPS has not yet been determined.