Publications

Alscher DM, Reimold F. New facts about encapsulating peritoneal sclerosis as a sequel of long-term peritoneal dialysis - what can we do? Minerva Urol Nefrol. 2007; 59:269-79.
Abstract. Full article.

Alscher DM, Braun N, Biegger D, Fritz P. Peritoneal mast cells in peritoneal dialysis patients, particularly in encapsulating peritoneal sclerosis patients. Am J Kidney Dis. 2007; 49:452-61.
Abstract. Full article.

Braun N. Encapsulating peritoneal sclerosis – an overview. Nephrol Ther. 2011.

Braun N. Difference in the expresion of hormone receptors and fibrotic markers in the human peritoneum - implications for therapeutic targets to prevent encapsulating peritoneal sclerosis. Perit Dial Int. 2011.

Braun N, Alscher DM, Fritz P, Edenhofer I, Kimmel M, Gaspert A, et al. Podoplanin-positive cells are a hallmark of encapsulating peritoneal sclerosis. Nephrol Dial Transplant. 2010.
Abstract. Full article.

Braun N, Alscher DM, Schwenger V, Amann K, Büttner M Deutsches peritoneal-biopsie register (dpr) – klinische und pathomorphologische aspekte. Der Nephrologe. 2010;5(6):531-534.
Full article.

Braun N, Kimmel M, Biegger D, Fritz P, Alscher DM. Angiogenesis and cellularity in encapsulating peritoneal sclerosis. Nephrol Dial Transplant Plus. 2010; 3:414-415.
Full article.

Braun N, Reimold F, Biegger D, Fritz P, Kimmel M, Ulmer C, et al. Fibrogenic growth factors in encapsulating peritoneal sclerosis. Nephron Clin Pract. 2009; 113:c88-95..
Abstract. Full article.

Fieren MW, Betjes MG, Korte MR, Boer WH. Posttransplant encapsulating peritoneal sclerosis: a worrying new trend? Perit Dial Int. 2007 Nov-Dec;27(6):619-24.
Abstract. Full article.

de Freitas D, Jordaan A, Williams R, Alderdice J, Curwell J, Hurst H, Hutchison A, Brenchley PE, Augustine T, Summers AM Nutritional management of patients undergoing surgery following diagnosis with encapsulating peritoneal sclerosis. Perit Dial Int. 2008 May-Jun;28(3):271-6.
Abstract. Full article.

Korte MR, Yo M, Betjes MG, Fieren MW, van Saase JC, Boer WH, Weimar W, Zietse R. Increasing incidence of severe encapsulating peritoneal sclerosis after kidney transplantation. Nephrol Dial Transplant. 2007 Aug;22(8):2412-4. Epub 2007 Mar 29.
Full article.

Korte MR, Boeschoten EW, Betjes MGH, on behalf of the EPS registry. The Dutch EPS Registry: Increasing the knowledge of encapsulating peritoneal sclerosis. Neth J of Medicine 2009 Sept; 67 (8): 359-362.
Abstract. Full article.

Korte MR, Sampimon DE, Betjes MG, Krediet RT. Encapsulating Peritoneal Sclerosis; the state of affairs. Nat Rev Nephrol. 2011 Aug 2;7(9):528-38.
Abstract. Full article.

Korte MR, Fieren MW, Sampimon DE, Lingsma HF, Weimar W, Betjes MG, investigators of the Dutch multicentre EPS study. Tamoxifen is associated with lower mortality of encapsulating peritoneal sclerosis: results of the Dutch multicentre EPS study. Nephrol Dial Transplant. 2011 Feb;26(2):691-7.
Abstract. Full article.

Korte MR, Habib SM, Lingsma H, Weimar W, Betjes MG. Posttransplantation encapsulating peritoneal sclerosis contributes significantly to mortality after kidney transplantation. Am J Transplant 2011 Mar;11(3):599-605.
Abstract. Full article.

Korte MR, Sampimon DE, Lingsma H, Fieren MW, Looman C, Zietse R, Weimar W, Betjes MG. Risk factors associated with encapsulating peritoneal sclerosis in Dutch EPS study. Perit Dial Int. 2011 May;31(3):269-278.
Abstract. Full article.

Saito A. Peritoneal dialysis in Japan: the issue of encapsulating peritoneal sclerosis and future challenges. Perit Dial Int. 2005 Apr;25 Suppl 4:S77-82.
Abstract. Full article.

Sampimon DE, Vlijm A, Phoa SS, Krediet RT, Struijk DG. Encapsulating peritoneal sclerosis in a peritoneal dialysis patient using biocompatible fluids only: is alport syndrome a risk factor? Perit Dial Int. 2010 Mar;30(2):240-2.
Full article.

Sampimon DE, Korte MR, Barreto DL, Vlijm A, de Waart R, Struijk DG, Krediet RT. Early diagnostic markers for encapsulating peritoneal sclerosis: a case-control study. Perit Dial Int. 2010 Mar;30(2):163-9. Epub 2010 Feb 1.
Abstract. Full article.

Schmidt DW, Flessner MF. Pathogenesis and treatment of encapsulating peritoneal sclerosis: basic and translational research. Perit Dial Int. 2008 Nov;28 Suppl 5:S10-5. Abstract. Full article.

Summers AM, Hoff CM, Topley N. How can genetic advances impact on experimental models of encapsulating peritoneal sclerosis? Perit Dial Int. 2008 Nov;28 Suppl 5:S16-20.
Abstract. Full article.

Summers AM. Encapsulating peritoneal sclerosis -- have we found the perpetrator?Perit Dial Int. 2009 Sep-Oct;29(5):499-501.
Full article.

Vlijm A, Stoker J, Bipat S, Spijkerboer AM, Phoa SS, Maes R, Struijk DG, Krediet RT. Computed tomographic findings characteristic for encapsulating peritoneal sclerosis: a case-control study. Perit Dial Int. 2009 Sep-Oct;29(5):517-22.
Abstract. Full article.

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New facts about encapsulating peritoneal sclerosis as a sequel of long-term peritoneal dialysis - what can we do?
Alscher DM, Reimold F. Minerva Urol Nefrol. 2007; 59:269-79.
Abstract A long lasting peritoneal dialysis (PD) leads to a special disease, so-called encapsulating peritoneal sclerosis (EPS). The hallmarks of the latter stages of the disease are intestinal obstructions and, as a consequence, malnourishment. For the precise diagnosis radiology and pathology are essential. (Triad “typical clinical picture- typical radiology- typical pathology”.) In the middle of the pathological process of EPS is proliferative fibrosis and sclerosis of the peritoneum that subsequently leads to the assembly of the typical “cocoon” and obstruction. In EPS we found in the peritoneum increased amounts of vascular endothelial growth factor (VEGF) fitting the hallmark of increased neoangiogenesis and blood exudates with fibrinous matrix on the peritoneum as a feeding ground for proliferation of fibroblasts. Additionally, the number of mast cells in EPS is decreased and therefore the chymase and other fibrinolytic enzymes. The “plasma-leak” hypothesis focuses on fibrin and our findings help to explain most of the pathophysiology. Since the mortality of EPS is still high, emphasis should be laid on preventive treatment. Since glucose and advanced glycation endproducts (AGEs), including glucose degradation products (GDPs), are responsible for fibrosis and sclerosis of the peritoneum, biocompatible peritoneal dialysis solutions with reduced amounts of AGEs and GDPs are recommended. Additionally, a careful monitoring of patients, especially after 5-8 years of PD is very important. In case of the first signs of EPS, cessation of the modality is necessary. Thanks to this approach, most end-stage EPS pictures can be avoided.

Peritoneal mast cells in peritoneal dialysis patients, particularly in encapsulating peritoneal sclerosis patients.
Alscher DM, Braun N, Biegger D, Fritz P. Am J Kidney Dis. 2007; 49:452-61.
Abstract BACKGROUND: We assumed that increased mast cell numbers contribute substantially to the fibrosis often seen in the peritoneum of peritoneal dialysis (PD) patients, particularly those with encapsulating peritoneal fibrosis (EPS). Therefore, we investigated mast cells in different pathological conditions of the peritoneum. METHODS: One hundred fifteen tissue probes with different peritoneal pathological states were selected (normal, n = 20; chronic appendicitis, n = 25; herniotomy, n = 24; fibrosis, n = 11; PD, n = 26; and EPS, n = 9). For staining of mast cells, we used alpha-naphtol-AS-d-chloracetate-esterase and mast cell tryptase. Next, we counted numbers of mast cells per square millimeter. Tryptase was measured by using image analysis. RESULTS: Measurements by means of both methods correlated well (r = 0.812). Numbers of mast cells per square millimeter were as follows: normal, 26 +/- 16; chronic appendicitis, 241 +/- 217; herniotomy, 115 +/- 88; fibrosis, 99 +/- 66; PD, 81 +/- 64, and EPS, 24 +/- 23 (P = 0.00006). Amounts of tryptase present were 2.900 +/- 0.118, 2.871 +/- 0.150, 2.733 +/- 0.183, 3.041 +/- 0.176, 2.780 +/- 0.184, and 2.609 +/- 0.234, respectively (P = 0.00002). CONCLUSION: We found upregulation of mast cells in specimens of chronic inflammatory diseases of the peritoneum. This also was true for PD patients, with the exclusion of patients with EPS. Therefore, loss-of-control functions of mast cells may contribute to the ill-understood disease entity of EPS.

Podoplanin-positive cells are a hallmark of encapsulating peritoneal sclerosis.
Braun N, Alscher DM, Fritz P, Edenhofer I, Kimmel M, Gaspert A, et al. Nephrol Dial Transplant. 2010.
Abstract BACKGROUND. 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. METHODS. 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. RESULTS. 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). CONCLUSIONS. 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.

Fibrogenic growth factors in encapsulating peritoneal sclerosis.
Braun N, Reimold F, Biegger D, Fritz P, Kimmel M, Ulmer C, et al. Nephron Clin Pract. 2009; 113:c88-95.
Abstract BACKGROUND: Increased local levels of fibrogenic growth hormones contribute substantially to the process of encapsulating peritoneal sclerosis (EPS) in animal models. METHODS: We analyzed probes from patients with normal kidney function (n = 10), with normal kidney function and inflammation (n = 10), on PD without (n = 10) and with EPS (n = 9). We investigated the degree of fibrosis and the number of vessels and vasculopathy. Additionally, we investigated the expression of NFkappaB, TGFbeta1, TGFbeta1 receptor, TGFbeta2, TGFbeta2 receptor, FGF-BP, CTGF and VEGF by immunohistochemistry. RESULTS: In EPS, we found an exclusive upregulation of VEGF (normal 0, appendicitis 1.0 +/- 1.2, PD 1.7 +/- 1.8 and EPS 5.7 +/- 4.4; p < 0.0001), whereas in PD, CTGF was significantly increased (normal 6.0 +/- 2.8, appendicitis 7.3 +/- 2.5, PD 10.0 +/- 1.8 and EPS 7.3 +/- 2.1; p = 0.0059). The results for the TGFbeta system and NFkappaB were not uniform, in EPS no increases were demonstrable. Vasculopathy was significantly more pronounced in EPS (normal 0.4 +/- 0.5, appendicitis 0.2 +/- 0.3, PD 1.0 +/- 0.7 and EPS 1.6 +/- 1.2; p < 0.0001) than in PD or inflammation (normal 30 +/- 16, appendicitis 82 +/- 48, PD 1,936 +/- 952 and EPS 2,613 +/- 1,209; p < 0.0001), whereas the density of vessels were decreased (normal 125 +/- 114, appendicitis 817 +/- 347, PD 81 +/- 57 and EPS 36 +/- 33; p < 0.0001). CONCLUSIONS: The process of EPS was associated with increased VEGF in the peritoneum. The reduced density of vessels compared with marked fibrosis could point to hypoxia as an inducer.

Posttransplant encapsulating peritoneal sclerosis: a worrying new trend?
Fieren MW, Betjes MG, Korte MR, Boer WH. Perit Dial Int. 2007 Nov-Dec;27(6):619-24.
Abstract Encapsulating peritoneal sclerosis (EPS) is a rare but serious complication in patients on peritoneal dialysis (PD). We describe a cluster of 13 EPS cases occurring in 2 university hospitals in The Netherlands. Most of these cases were diagnosed after recent kidney transplantation, when the patients developed severe symptoms of bowel obstruction. This accumulation raised the question as to whether other than known risk factors, such as duration of PD treatment, could be involved in the development or course of EPS after transplantation. According to various publications, EPS has been diagnosed often after withdrawal from PD, suggesting that cessation in itself may be a risk factor. In addition, transplantation-related management should be considered to play a role, including the use of the profibrotic calcineurin inhibitors and the trend to reduce the load of corticosteroids in treatment regimes. To identify risk factors, further multicenter studies are required, paying special attention to alterations in immunosuppressive treatment regimens as well as PD prescriptions, including PD fluid characteristics. Transfer from PD to hemodialysis should be under serious consideration in patients eligible for kidney transplantation as soon as there are indications of ultrafiltration failure.

Nutritional management of patients undergoing surgery following diagnosis with encapsulating peritoneal sclerosis.
de Freitas D, Jordaan A, Williams R, Alderdice J, Curwell J, Hurst H, Hutchison A, Brenchley PE, Augustine T, Summers AM. 2008 May-Jun;28(3):271-6.
Abstract BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a rare but serious complication of peritoneal dialysis (PD). Gastrointestinal (GI) symptoms affect appetite and dietary intake. Adequate nutrition is especially important if surgical interventions are required. Aim: To investigate the nutritional management of 23 EPS patients that underwent surgical intervention between 1999 and 2005 at Manchester Royal Infirmary, United Kingdom. METHODS: EPS was recognized by GI symptoms and diagnostically confirmed by laparotomy, computed tomographic scanning, or biopsy. RESULTS: Mean time on PD was 74 months (interquartile range 42-89 months). During the 12 months pre-diagnosis, 65% of the group showed significant weight loss (p = 0.0001), with 8 patients losing >10% of body weight; 74% of patients experienced significant albumin decrease (p = 0.001); and 56% of patients experienced GI symptoms during the 6 months pre-diagnosis. Nasogastric (NG) feeding was recommended for 8 patients but continued in only 1. 15 patients (mean albumin 27 g/L) commenced parenteral nutrition (PN); 9 patients recovered, with albumin increasing over the 6-month follow-up. Mean hospital time was 62 days for the group receiving neither NG nor PN, compared with 124.3 for the PN/NG group (p = 0.04). In patients that died of EPS, albumin continued to fall at 3 months post-diagnosis. CONCLUSION: There is currently little guidance for nutritional management of EPS. From this study we recommend (1) a high level of clinical suspicion for EPS, especially if PD patients have weight loss; (2) PN may be better than NG feeding but further studies into dual enteral nutrition and PN are needed; (3) aggressive nutritional supplementation pre- and postoperatively; and (4) dietitians need to recognize the high risk of refeeding syndrome.

The Dutch EPS Registry: Increasing the knowledge of encapsulating peritoneal sclerosis.
Korte MR, Boeschoten EW, Betjes MGH, on behalf of the EPS registry. Neth J of Medicine 2009 Sept; 67 (8): 359-362.
Abstract Encapsulating peritoneal sclerosis (EPS) is a rare condition characterised by fibrotic thickening of the visceral peritoneum, leading to encapsulating of the intestines with partial or total intestinal obstruction. EPS is a serious complication of peritoneal dialysis (PD) with high morbidity and a mortality exceeding 50%. At present, there is uncertainty concerning the incidence and the risk factors involved in the development of EPS . To address these questions a nationwide registry has been initiated. The primary goals of the registry are to record the incidence of EPS and investigate the association of different variables, such as PD duration, medication, dialysis solutions and kidney transplantation with EPS. The registry will improve the knowledge of EPS and will serve to develop guidelines and necessary management strategies. From the registry different research activities can be initiated. A major challenge lies in the establishment of criteria that allow a timely diagnosis of EPS. At present, there are no diagnostic tools that can accurately detect EPS at an early stage. For this reason, besides patients with proven EPS, the clinical suspicion of EPS will be a sufficient criterion for inclusion in the registry. This nationwide EPS registry is currently enrolling patients.

Encapsulating Peritoneal Sclerosis; the state of affairs.
Korte MR, Sampimon DE, Betjes MG, Krediet RT. Nat Rev Nephrol. 2011 Aug 2;7(9):528-38.
Abstract 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.

Tamoxifen is associated with lower mortality of encapsulating peritoneal sclerosis: results of the Dutch multicentre EPS study.
Korte MR, Fieren MW, Sampimon DE, Lingsma HF, Weimar W, Betjes MG, investigators of the Dutch multicentre EPS study. Nephrol Dial Transplant. 2011 Feb;26(2):691-7.
Abstract BACKGROUND:Encapsulating peritoneal sclerosis (EPS) is a serious complication of peritoneal dialysis (PD) with an increasing incidence. There is no clear consensus on the treatment of EPS, but anecdotal reports indicate improvement in EPS patients treated with tamoxifen. At present, there is no evidence for the effect of tamoxifen treatment in EPS patients. This study investigates the effect of treatment with tamoxifen on survival in EPS patients. METHODS:This study is a retrospective analysis of survival in EPS patients as part of the Dutch multicentre EPS study in the period January 1996 to July 2007. Sixty-three patients with severe EPS were followed up until August 2008. Demographic, patient and PD-related variables of EPS patients were investigated. Patients treated with tamoxifen were compared to patients not treated with tamoxifen. Survival was analysed with multivariate Cox regression analysis. RESULTS:Twenty-four patients were treated with tamoxifen, and 39 were not treated with tamoxifen. The clinical and demographic characteristics were similar for the tamoxifen-treated and non-treated groups. The mortality rate was significantly lower in tamoxifen-treated patients compared to EPS patients not treated with tamoxifen (45.8% vs 74.4%, P=0.03). Survival in tamoxifen-treated patients, adjusted for calendar time, age, use of corticosteroids, presence of functioning transplantation, use of parental nutrition and centre influences was longer in comparison to not-treated patients (HR 0.39, P=0.056). CONCLUSIONS:Tamoxifen treatment in EPS patients is associated with lower mortality and shows a trend to an increased multivariate-adjusted survival. This supports additional use of tamoxifen to treat patients with severe EPS.

Posttransplantation encapsulating peritoneal sclerosis contributes significantly to mortality after kidney transplantation.
Korte MR, Habib SM, Lingsma H, Weimar W, Betjes MG. Am J Transplant 2011 Mar;11(3):599-605.
Abstract Encapsulating peritoneal sclerosis (EPS) is a severe complication of peritoneal dialysis (PD) and may present after kidney transplantation, a condition known as posttransplantation EPS. The prevalence and impact of posttransplantation EPS on survival after kidney transplantation is unknown. From January 1, 1996 until July 1, 2007, 1241 PD patients were transplanted. Thirty-eight cases of posttransplantation EPS (3%) were identified from the Dutch multicenter EPS study. In EPS patients the mean pretransplant dialysis duration was longer than in the controls (71.4 ± 37.5 months vs. 34.7 ± 25.5, p < 0.0001). The majority of EPS cases were observed within the first 2 years after transplantation, but some cases appeared many years after transplantation. Two hundred and one (16.2%) patients died after transplantation, of which 17 were EPS patients. After infection (23.9%), cardiovascular disease (21.9%) and malignancy (10.9%), EPS (8.5%) was the fourth known cause of death after transplantation. Kaplan-Meier analysis showed a significant decreased survival for transplanted patients with posttransplantation EPS compared to transplanted patients without EPS. In conclusion, posttransplantation EPS is rare but carries a high mortality. A prolonged clinical vigilance and a high index of suspicion for the diagnosis are warranted, specifically in PD patients with a relatively long cumulative pretransplant duration of PD.

Risk factors associated with encapsulating peritoneal sclerosis in Dutch EPS study.
Korte M, Sampimon DE, Lingsma H, Fieren MW, Looman C, Zietse R, Weimar W, Betjes MG. Perit dial int. Int. 2011 May;31(3):269-278.
Abstract OBJECTIVE: Encapsulating peritoneal sclerosis (EPS) is a serious complication of peritoneal dialysis (PD) with a multifactorial pathophysiology and possible increasing incidence. The aim of the present study was to evaluate the independent associations of PD duration, age, dialysis fluids, and kidney transplantation with EPS. METHODS: A multicenter case-control study was performed in the Netherlands from 1 January 1996 until 1 July 2007. The population comprised 63 patients with EPS and 126 control patients. Control patients were selected from the national registry and were matched for date of PD start. Associations were analyzed using a log linear regression model. Primary outcome was appearance of EPS. RESULTS: Compared with control patients, patients with EPS were younger at the start of PD (34.7 ± 15.4 years vs. 51.5 ± 14.7 years, p < 0.0001). The cumulative period on PD was longer in EPS patients than in control patients (78.7 ± 37.8 months vs. 32.8 ± 24 months, p < 0.0001), and the cumulative period on icodextrin was also longer in EPS patients (32.7 ± 23.3 months vs. 18.1 ± 15.7 months, p = 0.006). Compared with control patients, more EPS patients underwent kidney transplantation (47 vs. 59, p < 0.0001). With regard to the period after transplantation, the yearly probability of EPS increased in the year after transplantation to 7.5% from 1.75%. In multivariate regression analysis, cumulative PD duration, age at PD start, transplantation, time from last transplantation to EPS, calendar time, time on icodextrin, and ultrafiltration failure were independently associated with EPS. Transfer from PD to hemodialysis for reasons other than suspected EPS could not be identified as a risk factor for EPS. CONCLUSIONS:Duration of PD, age at PD start, kidney transplantation, time since last transplantation, ultrafiltration failure, and time on icodextrin were associated with a higher risk of EPS.

Peritoneal dialysis in Japan: the issue of encapsulating peritoneal sclerosis and future challenges.
Saito A. Perit Dial Int. 2005 Apr;25 Suppl 4:S77-82.
Abstract Encapsulating peritoneal sclerosis (EPS) is a life-threatening complication of peritoneal dialysis (PD). The overall prevalence of EPS in Japanese PD patients is 2.3%. Among patients on PD for less than 5 years, the rate is 0.9%; among patients on PD for 5 - 10 years, the rate is 3.8%; and among patients on PD for >10 years, it is 11.5%. Thus, the longer the treatment duration, the higher the prevalence of EPS. Encapsulating peritoneal sclerosis does not result solely from the natural progression of peritoneal sclerosis. A "second hit" event, such as bacterial peritonitis, abdominal bleeding, or abdominal surgery may be needed to trigger the onset of EPS in the face of advanced peritoneal sclerosis. To prevent development of EPS, PD treatment is replaced by other treatments when patients reached high-transport status. Peritoneal lavage and prednisolone administration have been reported to be effective in preventing or stopping the progress of EPS. When bowel obstruction has occurred, total enterolysis to remove the fibrous capsule from the bowel is indicated. To maximize overall quality of life, patients with endstage renal disease (ESRD) should have the choice to make use of all the treatment modalities available: PD, hemodialysis (HD), and transplantation. Furthermore, the development of truly biocompatible PD equipment--including peritoneal catheters, solutions, and systems--are desirable to extend PD treatment for the long-term. The cost of individual products could decrease significantly if PD use were to increase to 30% from 10% among ESRD patients worldwide. As practitioners, we have to further improve the technical survival rate and functional duration of PD treatment so that adequate peritoneal function can be maintained for 10 years in at least 40% of PD patients. The goal is to place PD on par with HD using high-flux dialysis membranes and ultrapure dialysis solution.

Early diagnostic markers for encapsulating peritoneal sclerosis: a case-control study.
Sampimon DE, Korte MR, Barreto DL, Vlijm A, de Waart R, Struijk DG, Krediet RT.Perit Dial Int. 2010 Mar;30(2):163-9. Epub 2010 Feb 1.
Abstract OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Pathogenesis and treatment of encapsulating peritoneal sclerosis: basic and translational research.
Schmidt DW, Flessner MF. Perit Dial Int. 2008 Nov;28 Suppl 5:S10-5.
Abstract Encapsulating peritoneal sclerosis is a devastating condition in long-term peritoneal dialysis patients. Animal models have employed chemical insults to simulate its pathology and have provided insights into its pathophysiology, which appears to include inflammation, angiogenesis, and fibrosis. Monitoring of biomarkers and interruption of molecular pathways have provided potential interventions to slow or prevent the disease process. However, there remain many questions concerning the trigger that alters chronic peritoneal inflammation in peritoneal dialysis to severe sclerosis, peritoneal adhesions, and bowel obstruction. Further advances in therapy will likely require an effective means of an early diagnosis through related biomarkers, which in turn will require further advances in the understanding of the pathogenesis of this disease process.

How can genetic advances impact on experimental models of encapsulating peritoneal sclerosis?
Summers AM, Hoff CM, Topley N. Perit Dial Int. 2008 Nov;28 Suppl 5:S16-20.
Abstract In this review we discuss how animal models have contributed to the understanding of pathological pathways that may be involved in the development of encapsulating peritoneal sclerosis. We review the various interventional procedures that, so far, have ameliorated disease progression in animals. Reviewing advancements in molecular biology and genetic technologies, we discuss how future experimental models may impact our understanding of the pathogenesis and treatment of this rare but complex disease.

Computed tomographic findings characteristic for encapsulating peritoneal sclerosis: a case-control study.
Vlijm A, Stoker J, Bipat S, Spijkerboer AM, Phoa SS, Maes R, Struijk DG, Krediet RT. Perit Dial Int. 2009 Sep-Oct;29(5):517-22.
Abstract BACKGROUND: Computed tomography (CT) is often used to confirm the diagnosis of encapsulating peritoneal sclerosis (EPS) but there is no consensus on specific CT abnormalities. To establish CT findings characteristic for EPS, we compared CT findings between EPS patients and long-term peritoneal dialysis (PD) patients without EPS. METHODS: We included as cases all EPS patients in our center from 1996 to 2008 that underwent a CT scan at the time of diagnosis. Controls were all other long-term PD patients (PD duration > or = 4 years) without EPS that had a CT scan for different reasons. The CT scans were blindly and independently reviewed by 3 radiologists: 2 abdominal radiologists with PD knowledge (Observers 1 and 2) and 1 radiologist without PD experience (Observer 3). RESULTS: We included 15 EPS patients and 16 controls. Observer 1 found 6 CT findings that were significantly more often present in EPS than in controls (p < or = 0.05): peritoneal enhancement, thickening, and calcifications; adhesions of bowel loops; signs of obstruction; and fluid loculation/septation. Observer 2 scored almost identically but Observer 3 scored differently. The sensitivity and specificity of a combination of specific CT findings were, respectively, 100% and 94% for Observers 1 and 2, and 79% and 88% for Observer 3. CONCLUSION: CT scans showed characteristic abnormalities that were significantly more often present in EPS patients compared to long-term PD control patients. CT can be used to confirm the diagnosis of EPS when experienced radiologists apply a combination of specific CT findings.