Significant Decreasing Incidence of Encapsulating Peritoneal Sclerosis in the Dutch Population of Peritoneal Dialysis Patients.

The Dutch Encapsulating Peritoneal Sclerosis (EPS) Registry was started in 2009. Cases were identified by contacting all Dutch nephrologists twice yearly. The predefined criteria for EPS allowed for inclusion of patients with diagnosed and suspected EPS. Cases registered between January 2009 and January 2015 were analyzed with follow-up until September 2015. Fifty-three EPS cases were identified, of which 28.3% were post-transplantation EPS cases. Fourteen patients were initially categorized as suspected EPS, of whom 13 developed EPS. A remarkable 6-fold decrease in the yearly incidence of EPS was observed, from 0.85% in 2009 to 0.14% in 2014. This decrease could not be explained by a decrease in the number of PD patients or average duration of PD treatment in this period. Two-year survival of EPS patients was 52%. The use of tamoxifen and surgical interventions increased significantly over the years. Tamoxifen-treated cases showed a trend to better patient survival and post-transplantation EPS had a significantly favorable outcome. In conclusion, the incidence of EPS has declined significantly in the Netherlands from 2009 to 2014.

CD4-Positive T Cells and M2 Macrophages Dominate the Peritoneal Infiltrate of Patients with Encapsulating Peritoneal Sclerosis.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a severe complication of peritoneal dialysis (PD). Previously, it has been shown that infiltrating CD4-positive T cells and M2 macrophages are associated with several fibrotic conditions. Therefore, the characteristics of the peritoneal cell infiltrate in EPS may be of interest to understand EPS pathogenesis. In this study, we aim to elucidate the composition of the peritoneal cell infiltrate in EPS patients and relate the findings to clinical outcome. STUDY DESIGN, SETTING, AND PARTICIPANTS: We studied peritoneal membrane biopsies of 23 EPS patients and compared them to biopsies of 15 PD patients without EPS. The cellular infiltrate was characterized by immunohistochemistry to detect T cells (CD3-positive), CD4-positive (CD4+) and CD8-positive T cell subsets, B cells (CD20-positive), granulocytes (CD15-positive), macrophages (CD68-positive), M1 (CD80-positive), and M2 (CD163-positive) macrophages. Tissues were analysed using digital image analysis. Kaplan-Meier survival analysis was performed to investigate the survival in the different staining groups. RESULTS: The cellular infiltrate in EPS biopsies was dominated by mononuclear cells. For both CD3 and CD68, the median percentage of area stained was higher in biopsies of EPS as opposed to non-EPS patients (p<0.001). EPS biopsies showed a higher percentage of area stained for CD4 (1.29% (0.61-3.20)) compared to CD8 (0.71% (0.46-1.01), p = 0.04), while in the non-EPS group these cells were almost equally represented (respectively 0.28% (0.05-0.83) versus 0.22% (0.17-0.43), p = 0.97). The percentage of area stained for both CD80 and CD163 was higher in EPS than in non-EPS biopsies (p<0.001), with CD163+ cells being the most abundant phenotype. Virtually no CD20-positive and CD15-positive cells were present in biopsies of a subgroup of EPS patients. No relation was found between the composition of the mononuclear cell infiltrate and clinical outcome. CONCLUSIONS: A characteristic mononuclear cell infiltrate consisting of CD4+ and CD163+ cells dominates the peritoneum of EPS patients. These findings suggest a role for both CD4+ T cells and M2 macrophages in the pathogenesis of EPS.

Patients with encapsulating peritoneal sclerosis have increased peritoneal expression of connective tissue growth factor (CCN2), transforming growth factor-ß1, and vascular endothelial growth factor.

INTRODUCTION: Encapsulating peritoneal sclerosis (EPS) is a devastating complication of peritoneal dialysis (PD). The pathogenesis is not exactly known and no preventive strategy or targeted medical therapy is available. CCN2 has both pro-fibrotic and pro-angiogenic actions and appears an attractive target. Therefore, we studied peritoneal expression of CCN2, as well as TGFß1 and VEGF, in different stages of peritoneal fibrosis. MATERIALS AND METHODS: Sixteen PD patients were investigated and compared to 12 hemodialysis patients and four pre-emptively transplanted patients. Furthermore, expression was investigated in 12 EPS patients in comparison with 13 PD and 12 non-PD patients without EPS. Peritoneal tissue was taken during kidney transplantation procedure or during EPS surgery. In a subset of patients, CCN2 protein levels in peritoneal effluent and plasma were determined. Samples were examined by qPCR, histology, immunohistochemistry, and ELISA. RESULTS: Peritoneal CCN2 expression was 5-fold higher in PD patients compared to pre-emptively transplanted patients (P < 0.05), but did not differ from hemodialysis patients. Peritoneal expression of TGFß1 and VEGF were not different between the three groups; neither was peritoneal thickness. Peritoneum of EPS patients exhibited increased expression of CCN2 (35-fold, P < 0.001), TGFß1 (24-fold, P < 0.05), and VEGF (77-fold, P < 0.001) compared to PD patients without EPS. In EPS patients, CCN2 protein was mainly localized in peritoneal endothelial cells and fibroblasts. CCN2 protein levels were significantly higher in peritoneal effluent of EPS patients compared to levels in dialysate of PD patients (12.0 ± 4.5 vs. 0.91 ± 0.92 ng/ml, P < 0.01), while plasma CCN2 levels were not increased. CONCLUSIONS: Peritoneal expression of CCN2, TGFß1, and VEGF are significantly increased in EPS patients. In early stages of peritoneal fibrosis, only CCN2 expression is slightly increased. Peritoneal CCN2 overexpression in EPS patients is a locally driven response. The potential of CCN2 as biomarker and target for CCN2-inhibiting agents to prevent or treat EPS warrants further study.

Histological and clinical findings in patients with post-transplantation and classical encapsulating peritoneal sclerosis: a European multicenter study.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) commonly presents after peritoneal dialysis has been stopped, either post-transplantation (PT-EPS) or after switching to hemodialysis (classical EPS, cEPS). The aim of the present study was to investigate whether PT-EPS and cEPS differ in morphology and clinical course. METHODS: In this European multicenter study we included fifty-six EPS patients, retrospectively paired-matched for peritoneal dialysis (PD) duration. Twenty-eight patients developed EPS after renal transplantation, whereas the other twenty-eight patients were classical EPS patients. Demographic data, PD details, and course of disease were documented. Peritoneal biopsies of all patients were investigated using histological criteria. RESULTS: Eighteen patients from the Netherlands and thirty-eight patients from Germany were included. Time on PD was 78(64-95) in the PT-EPS and 72(50-89) months in the cEPS group (p>0.05). There were no significant differences between the morphological findings of cEPS and PT-EPS. Podoplanin positive cells were a prominent feature in both groups, but with a similar distribution of the podoplanin patterns. Time between cessation of PD to the clinical diagnosis of EPS was significantly shorter in the PT-EPS group as compared to cEPS (4(2-9) months versus 23(7-24) months, p<0.001). Peritonitis rate was significantly higher in cEPS. CONCLUSIONS: In peritoneal biopsies PT-EPS and cEPS are not distinguishable by histomorphology and immunohistochemistry, which argues against different entities. The critical phase for PT-EPS is during the first year after transplantation and therefore earlier after PD cessation then in cEPS.

Localized encapsulating peritoneal sclerosis constricting the terminal ileum--an unusual appearance requiring surgical intervention.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a rare complication of peritoneal dialysis (PD). It is characterized by encapsulation of the bowel, causing symptoms of intestinal obstruction. Exclusive involvement of parts of the bowel may occur and may be more common than previously thought. Our main objective was to investigate and report on patients with localized EPS. METHODS: Between July 2002 and December 2011, 9 of 17 EPS patients were referred to our department of surgery for a diagnostic laparotomy. Three of the 9 cases showed localized encapsulation of the small bowel and were selected for the purpose of this study. RESULTS: All 3 patients presented with an acute inflammatory state and symptoms of bowel obstruction. In 2 patients, EPS became clinically overt after kidney transplantation; the third patient was diagnosed while on hemodialysis. All shared a history of PD ranging from 31 to 101 months. In none of the patients was radiologic examination conclusive, although 2 showed peritoneal thickening and ascites. Each patient underwent laparotomy, confirming EPS. In all cases, a thickened peritoneal membrane became apparent, predominantly covering the ileocecal region of the intestine. In addition, a constrictive membrane at the level of the terminal ileum was noted. In 2 cases, the patients underwent enterolysis and dissection of the constricting fibrotic peritoneal membrane (peritonectomy) without bowel resection. The 3rd patient was managed with parenteral nutrition and tamoxifen. The postoperative course in 1 patient was complicated by infected ascites that resolved with antibiotic treatment. Eventually, all patients were doing well, with adequate oral intake and without the need for repeat surgery. CONCLUSIONS: Localized EPS may be more common than previously thought. It has a predilection for the level of the terminal ileum. We believe that an elective diagnostic laparotomy should be considered early, because this procedure offers both diagnostic opportunities and therapeutic options. Localized EPS cases may benefit most from enterolysis and peritonectomy.

Lower mortality and inflammation from post-transplantation encapsulating peritoneal sclerosis compared to the classical form.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) may occur after kidney transplantation (post-transplantation EPS) or may be diagnosed during or after peritoneal dialysis treatment (classical EPS). The aim of the present study was to investigate to what extent both EPS entities differ in clinical presentation, radiological findings, outcome, and the systemic inflammatory response, as measured by plasma C-reactive protein (CRP) levels both prior to and after EPS diagnosis. METHODS: We performed a retrospective analysis of 15 post-transplantation EPS and 19 classical EPS patients who were diagnosed at seven hospitals in the Netherlands between January 1, 2000, and January 1, 2011. RESULTS: There were no inter-group differences in age, duration of peritoneal dialysis, clinical presentation, or radiology findings at diagnosis. Post-transplantation patients had experienced a lower number of peritonitis episodes per patient-year (0.2 (0.0-0.4) vs. 0.7 (0.3-1.2), p = 0.01) with a longer interval between the last peritonitis and EPS diagnosis (18.1 (4.6-34.3) vs. 4.4 (0.89-13.78) months, p = 0.01). Post-transplantation EPS patients showed a remarkably lower mortality rate (40.0 vs. 84.2%, p < 0.05). In both groups a pattern of elevated CRP values was observed, increasing within the year before EPS diagnosis. In the post-transplantation group the median CRP level at diagnosis was lower (56.0 vs. 144.50 mg/l, p < 0.05) than in the classical EPS group. CONCLUSION: Post-transplantation EPS has a similar clinical presentation as classical EPS but with a lower systemic inflammatory response and better outcome.