Encapsulating Peritoneal Sclerosis Group Research Articles

C allele in transforming growth factor-β1 rs1800471 gene polymorphisms might indicate a protective feature in encapsulating peritoneal sclerosis development.

Peritoneal fibrosis may progress in peritoneal dialysis (PD) patients to a fatal clinical condition called encapsulating peritoneal sclerosis (EPS). Transforming growth factor (TGF)-β plays a pivotal role in the pathogenesis of peritoneal fibrosis. We aimed to investigate the association among polymorphisms in the gene encoding TGF-β1, which were -509C/T (rs1800469), +869T/C (rs1982073), and +915G/C (rs1800471) in EPS patients. A total of 16 PD patients who were clinically and radiologically diagnosed with EPS were enrolled and 22 age- and gender-matched PD patients were selected as the non-EPS group. G allele frequency at the rs1800471 gene polymorphism was significantly higher in the EPS group than non-EPS group (p=0.005). Interestingly, the non-EPS group patients had CC or CG polymorphisms. C allele in TGF-β1 rs1800471 gene polymorphisms might indicate a protective feature in EPS development. Knowing the presence of polymorphism may be effective in selecting renal replacement therapy in patients.

Incidence and outcomes of encapsulating peritoneal sclerosis (EPS) and factors associated with severe EPS.

BackgroundEncapsulating peritoneal sclerosis (EPS) is a rare but serious complication of long-term peritoneal dialysis (PD). However, previous studies reported large variations in its mortality rates that may associate with a different degree of EPS severity. This study reports the incidence and outcomes of EPS and identifies the risk factors associated with severe EPS.MethodsWe retrospectively analyzed clinical data of EPS patients from 3 medical centers in Taiwan from January 1982 to September 2015, and classified patients as having mild/moderate or severe EPS. Patients with intractable intestinal obstruction/gut-related sepsis that needed surgical intervention or resulted in mortality were in severe EPS group. Follow-up for outcome was through December 31, 2015. Clinical characteristics, peritoneal dialysis (PD)-related parameters, biochemical and imaging results were analyzed and compared between groups.ResultsFifty-eight of 3202 patients undergoing PD during the study period had EPS (prevalence 1.8%). The incidence of EPS increased for patients on PD for >6–8 years (≤6 yrs. vs. >6–8 yrs., 0.0% vs. 1.8%, p = 0.001). Relative to those on PD for >6–8 years, the risk of EPS significantly increased with PD duration longer than 10 years (>10–12 years vs. >6–8 years: OR: 5.5, 95% CI: 1.7–17.1, p < 0.01). Twenty-three patients fulfilled the criteria for severe EPS. The overall mortality rate of EPS was 35% (20/58), and was 74% (17/23) in the severe EPS group. The average serum levels of C-reactive protein (CRP) and intact-parathyroid hormone (i-PTH), which were checked every 3~6 months within one year before diagnosis of EPS, were higher in severe EPS group than in mild/moderate group (p = 0.02, p = 0.08, respectively). Multivariate analysis revealed severe EPS was independently associated with bowel tethering (based on CT), presentation with bloody ascites, diagnosis of EPS after withdrawal from PD, and i-PTH ≥ 384 pg/mL. Receiver operating characteristic analysis indicated that presentation with 2 or more of the 5 risk factors (EPS diagnosis after PD withdrawal, bloody ascites, bowel tethering, CRP ≥ 29 mg/L, and i-PTH ≥ 384 pg/mL) had a good accuracy (AUC = 0.80, p = 0.001) for prediction of severe EPS.ConclusionsThe incidence of EPS increases with PD duration. Severe EPS has high mortality rate and is associated with bowel tethering, presentation of bloody ascites, diagnosis after PD withdrawal, and higher serum levels of i-PTH before EPS diagnosis. Having 2 or more of the 5 risk factors can provide a good accuracy for prediction of severe EPS.

Risk factors for encapsulating peritoneal sclerosis: Analysis of a 36‐year experience in a University Hospital

Encapsulating peritoneal sclerosis (EPS) is a rare but serious complication that occurs in peritoneal dialysis (PD) therapy. The present study aimed to identify the risk factors, especially peritonitis and biocompatible PD fluid. The study included 703 patients who received PD between January 1980 and March 2015 at two centres. The patients were divided into two groups: those who had developed EPS (EPS group: n = 44) and those who had no documentary evidence of EPS (non-EPS group: n = 659). The independent risks of EPS were determined by univariate and multivariate logistic models. Encapsulating peritoneal sclerosis occurred in 44/703 (6.3%) patients between January 1980 and March 2015. In multivariate logistic models of risk factors correlated with EPS, dialysate to plasma creatinine ratio (D/P Cr) by peritoneal equilibration test (PET) and history of peritonitis were risk factors for EPS development (P < 0.01, respectively) in addition to PD duration. Especially, total duration of peritonitis, defined by period between onset and resolution of peritonitis, was an important risk factor for EPS development in patients with a history of peritonitis. Receiver operating characteristic (ROC) curve analysis revealed that cut-off point for EPS development was 36 days. Moreover, biocompatible PD fluid contributed to decreased EPS development. Both the longer duration of peritonitis and higher D/P Cr, as well as the longer PD duration, were risk factors for EPS development. Furthermore, use of biocompatible PD fluid contributed to the decrease in EPS development.

Can radiological assessment of abdominal computerized scans diagnose encapsulating peritoneal sclerosis in long‐term peritoneal dialysis patients?

Encapsulating peritoneal sclerosis (EPS) is a rare but potentially devastating complication of long-term peritoneal dialysis (PD). Changes to the peritoneal membrane occur with duration of PD therapy. To determine the potential effect of prospective computerized tomography (CT) scanning, we reviewed the scans of patients who had developed EPS compared with those without EPS. We retrospectively compared CT scans that had been prospectively performed in a screening program for PD patients after 4 years of PD and compared scans from 18 patients with confirmed EPS and 26 vintage matched controls without EPS. Anonymized scans were reported independently by two blinded experienced radiologists. Peritoneal thickening, calcification, bowel tethering, thickening and dilatation were significantly more commonly reported in the EPS group. Total combined radiological scores, also including septation within peritoneal fluid, were significantly higher in the EPS group and the greatest for those who died as a consequence of EPS. Simplified scoring based on presence or absence, then for a score of ≥3.0, gave a receiver operating characteristic value of 0.87 for EPS, with a sensitivity of 78% and specificity of 85%, respectively. Inter-observer agreement varied from poor to good, being the greatest for calcification and bowel dilatation and the lowest for peritoneal thickening. CT scan reporting can differentiate EPS from peritoneal changes associated with duration of PD therapy. Severity of abnormalities was associated with clinical outcomes. However, inter-observer agreement varies with different radiological appearances, and future studies are required to determine weighting of radiological changes to provide prognostic information for clinicians and patients.

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.

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.

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.

The peritoneal osmotic conductance is low well before the diagnosis of encapsulating peritoneal sclerosis is made

Encapsulating peritoneal sclerosis (EPS) is a serious condition whose frequency is increasing the longer the duration of peritoneal dialysis. To identify prognostic indicators of EPS, we studied here longitudinal changes in peritoneal membrane function of patients who later developed this complication. We identified all patients with an unequivocal diagnosis of EPS who began their peritoneal dialysis in our unit over a 20-year period and matched each of them for dialysis duration and age with four control patients who completed their dialysis. The dialysate/plasma creatinine ratio increased with time in both groups but was significantly higher in the patients with EPS only at the time their dialysis was discontinued. The ultrafiltration capacity was significantly worse for at least 2 years before stopping dialysis, diverging further at the time dialysis ceased, suggesting reduced osmotic conductance in the EPS patients. Both the glucose exposure rate for the 5 years preceding stoppage of dialysis and exposure to the osmotic agent icodextrin were significantly higher. Residual renal function was less in the EPS group, but there was no significant difference in the rates of peritonitis compared to the control group. The 24 h peritoneal protein clearance was not significantly different in EPS patients, possibly due to a greater fibrous matrix. Thus, our study shows that regular peritoneal membrane function tests can identify most patients at high risk of developing EPS before its occurrence.

High-transport stateの長期持続状態は被嚢性腹膜硬化症の発症危険因子である―CAPD離脱前後での腹膜機能変化からの解析―

The pathophysiology of encapsulating peritoneal sclerosis (EPS) that develops after withdrawal from long-standing dependence on CAPD remains unclear. The aim of this study was to clarify the risk factors for EPS as expressed in the peritoneal function. Fourteen patients who had shifted to standard hemodialysis after long-term CAPD (average, 105 months) were studied: 3 developed EPS after PD withdrawal while 11 did not. Analysis of the data obtained from the peritoneal equilibration test (PET) revealed that: (1) the dialysate/plasma creatinine ratio (D/Pcr) was significantly higher in the EPS group than in the non-EPS group during the course of PD as well as after PD withdrawal; and (2) eight patients, including the 3 with EPS, were classified as being in a high-transport membrane state (HTS) at PD withdrawal. The duration of HTS during PD was longer in those patients with EPS. During the periods after PD withdrawal, none of these EPS patients recovered from HTS, whereas 4 of the 5 non-EPS patients did. These data suggest that long-standing HTS during the course of PD as well as post-withdrawal, may be risk factors for EPS development. For this reason, it is indicated that PET has clinical relevance in examining sequential changes in peritoneal function and in detecting those patients at risk of EPS.

Risk factors for developing encapsulating peritoneal sclerosis in the icodextrin era of peritoneal dialysis prescription

Encapsulating peritoneal sclerosis (EPS) is an uncommon but potentially devastating complication of peritoneal dialysis. We have observed an increased incidence in our centre over the last few years. To look at potential risk factors for developing EPS, we reviewed 39 cases diagnosed between 2000 and 2009 and compared these with a control group of 71 patients who had been treated by peritoneal dialysis for a minimum of 4 years. Both groups extensively used icodextrin, >80% of patients. Both groups had been treated by peritoneal dialysis for a similar time: EPS median 54 months (46-87.5), compared to controls 70 (54-79.5). However, more of the EPS group were treated with peritoneal cyclers (75% vs 46%, X(2) = 6.86, P = 0.009) and prescribed more peritoneal dialysate 14.2 l/day +/- 0.7 vs 10.8 +/- 0.5, P < 0.0001. Although both groups were fast transporters, those with EPS had higher D/P creatinine ratios on peritoneal equilibration testing, 0.84 +/- 0.1 vs 0.77 +/- 0.1, P < 0.05, and lower peritoneal test ultrafiltration volumes, 193 +/- 26 ml vs 283 +/- 21 ml, P < 0.05. Discussion. The patients in the EPS group were faster transporters, with lower peritoneal equilibration and 24-h ultrafiltration volumes, and were exposed to greater volumes of peritoneal dialysates compared to peritoneal dialysis vintage controls.

Serum ?2 microglobulin (?2MG) level is a potential predictor for encapsulating peritoneal sclerosis (EPS) in peritoneal dialysis patients

Encapsulating peritoneal sclerosis (EPS) is a serious complication in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) or automated peritoneal dialysis (APD). The aim of this study was to find a predictor for EPS. Patients with EPS who were detected by a historical cohort study using clinical data of 219 CAPD patients at our hospital. We recruited 25 patients with EPS who were compared with the patients without EPS who were matched for age and dialysis period as controls. Differences between the two groups (non-EPS group and EPS group) with respect to age, gender, primary disease, dialysis period, serum urea nitrogen, serum creatinine, beta2MG, CRP and PET (peritoneal equilibration test) category (determined by the peritoneal function testing) were analyzed. According to multiple regression analysis, a high beta2MG level was an independent risk factor for EPS (odds ratio 1.162, 95% confidence interval 1.026 - 1.317, p = 0.018). Other clinical markers did not show positive significance. A ROC (receiver operating characteristic) curve was prepared to evaluate the suitability of I(2)2MG measurement as a screening test. The sensitivity was 64% and the specificity was 80% when a beta2MG level of 37.0 mg/dl was taken as the cut-off value. The odds ratio for occurrence of EPS was 8.8 when beta2MG level was in the range of 35 - 40 mg/dl, 13.5 when I(2)2MG level was > 40 mg/dl and 1 when beta2MG level was < 30 mg/dl. These findings suggest that beta2MG is useful as a screening test for the onset of EPS, and that beta2MG and accumulation of middle-molecular uremic substances may be related to the pathophysiology of EPS.

Restoration of peritoneal integrity after withdrawal of peritoneal dialysis: characteristic features of the patients at risk of encapsulating peritoneal sclerosis

The epidemiological characteristics of encapsulating peritoneal sclerosis (EPS), such as its high incidence in patients with long-term peritoneal dialysis (PD) treatment, and the onset of EPS after patients are switched to hemodialysis (HD) may indicate an activated pathological process after PD withdrawal, especially in long-term PD patients. Accordingly, we aimed to observe changes in peritoneal function after the stoppage of PD, and to clarify the characteristic features of the patients at risk of EPS. Thirty-three patients who were switched from continuous ambulatory peritoneal dialysis (CAPD) to HD were enrolled in this trial. Changes in the dialysate/plasma creatinine (D/P Cr) and CA125 levels in the effluent of the peritoneal equilibration test were observed for 6 months. Furthermore, each patient was followed-up for 36 months after PD withdrawal to monitor for the development of EPS. D/P Cr decreased significantly, while CA125 levels tended to increase. Nine patients developed EPS during the follow-up period and they specifically showed significant increases of D/P Cr levels and significantly lower levels of CA125 at PD withdrawal. The accumulation of high transporters in the EPS group at 0 and 6 months after PD withdrawal was significant. Peritoneal recovery may take place after withdrawal from PD treatment and such recover indicated by improvement of transport states and a rise of the CA125 level. The present study revealed that a high-transport state and lack of increase of CA125 in the effluent were associated with EPS development after PD withdrawal. This may suggest that the lack of peritoneal recovery after PD withdrawal is predictive for EPS development.

Possible pathologic involvement of receptor for advanced glycation end products (RAGE) for development of encapsulating peritoneal sclerosis in Japanese CAPD patients

Encapsulating peritoneal sclerosis (EPS) is a serious complication of PD. The cause(s) of EPS are unknown but may include peritonitis and long duration of PD treatment. However, EPS may also develop in some patients without a history of peritonitis or with rather short duration of PD therapy. It has been suggested that an increasing peritoneal solute transport rate (PSTR) as a function of time on PD treatment is a risk factor for EPS development after transfer to hemodialysis, and that high PSTR is associated with an increased peritoneal microvessels surface area. Other putative mechanisms might include advanced glycated end products (AGE) and their receptors, RAGE. The purpose of this study was to investigate genetic variations in PD patients developing EPS in comparison to PD patients without EPS. SNPs in genes related to angiogenesis as well as RAGE were analyzed. Twenty patients (M/F: 12/8, mean age at start of PD 42.2 years, mean duration of PD 8.4 years) who were diagnosed as EPS during the period 1982 - 2002 at Jikei University Hospital and a matched control group (n = 20) of nonEPS PD patients were studied. The following 5 SNPs were analyzed: VEGF 936 C/T, ecNOS -786 T/C, 298 Glu/Asp, and RAGE -374 T/A, and -429 T/C. The SNPs were analyzed by the pyrosequencing method. The C allele (T/C and C/C) in the RAGE -429T/C genotype was not found in any of the EPS patients (EPS, T/T: 20/20 (100%), nonEPS, T/T: 15/20 (75%), T/C: 4/20 (20%), C/C: 1/2 0(5%), nonC allele vs C allele, p = 0.013), although every allele was found in other SNPs. We conclude that these preliminary data show that whereas genotypes directly related to angiogenesis did not differ between EPS and nonEPS patients, it is noteworthy that no patients in the EPS group had a C allele in the RAGE -429T/C genotype. This might indicate a possible genetic contribution to the development of EPS that is related to RAGE.