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

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1 Encapsulating peritoneal sclerosis Lin JL, Lin-Tan DT, Hsu KH et al. Environmental lead exposure and progression of chronic renal diseases in patients without diabetes. N Engl J Med 2003; 348: Lin-Tan DT, Lin JL, Yen TH et al. Long-term outcome of repeated lead chelation therapy in progressive non-diabetic chronic kidney diseases. Nephrol Dial Transplant 2007; 22: Krachler M, Wirnsberger GH. Long-term changes of plasma trace element concentrations in chronic hemodialysis patients. Blood Purif 2000; 18: Colleoni N, Arrigo G, Gandini E et al. Blood lead in hemodialysis patients. Am J Nephrol 1993; 13: Kessler M, Durand PY, Huu TC et al. Mobilization of lead from bone in end-stage renal failure patients with secondary hyperparathyroidism. Nephrol Dial Transplant 1999; 14: Lin JL, Lin-Tan DT, Yen TH et al. Blood lead levels, malnutrition, inflammation, and mortality in patients with diabetes treated by long-term hemodialysis. 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Circulation 2006; 114: Received for publication: ; Accepted in revised form: Risk factors for developing encapsulating peritoneal sclerosis in the icodextrin era of peritoneal dialysis prescription Anne-Marie Habib 1, Emma Preston 1 and Andrew Davenport 2 1 University College London Center for Nephrology, Royal Free Hospital, Pond Street, and 2 UCL Center for Nephrology, Royal Free Campus, University College London Medical School, London, UK Correspondence and offprint requests to: Andrew Davenport; Andrew.davenport@royalfree.nhs.uk Abstract Background. 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. Methods and patients. 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. Results. Both groups had been treated by peritoneal dialysis for a similar time: EPS median 54 months ( ), compared to controls 70 ( ). 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 < 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 < The Author Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. 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2 1634 A.-M. Habib et al. 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. Keywords: encapsulating peritoneal sclerosis; glucose; icodextrin; peritoneal dialysis Introduction More than 100,000 patients with end-stage kidney disease are treated by various forms of peritoneal dialysis (PD) worldwide. Although a successful technique, peritoneal dialysis is not usually a long-term treatment option, as many patients who are not transplanted most commonly convert to haemodialysis following episodes of peritonitis [1] or ultrafiltration failure, particularly once residual renal function has been lost. For those patients who remain on peritoneal dialysis, encapsulating peritoneal sclerosis (EPS) is an uncommon but potentially life-threatening complication of long-term peritoneal dialysis. The first reports of EPS appeared from North America more than 25 years ago [2]. Subsequently, more cases have been reported from Japan; this may be because of the lower transplantation rate coupled with reduced cardiovascular mortality and low rates of peritonitis, such that patients remain on peritoneal dialysis therapy for longer time periods than in other countries. A 4-year prospective multi-centre study of almost 2000 patients in Japan reported an increasing incidence and mortality rate for EPS with increasing longevity of treatment, increasing progressively from 0.7% after 3 years to 2.1% after 5 years, to 5.8% after 10 years and 17.2% in patients who had been treated for more than 15 years, with a corresponding mortality from EPS increasing progressively from 0% to 8.3%, 61.5% and 100%, respectively [3]. The underlying pathophysiological aetiology of EPS remains to be determined, as it can present acutely but equally may have a chronic insidious course and can be triggered by an episode of acute peritonitis [4] but also post-renal transplantation [5]. As such, apart from the duration of peritoneal dialysis, other potential risk factors for developing EPS have been suggested, including peritoneal transport status [6], repeated episodes of peritonitis, drugs and exit site preparations, such as chlorhexidine [7], peritoneal exposure to hyperosmolar glucose solutions, glucose degradation products and advanced glycosylation end products. Earlier studies from Japan and Australia [4, 8] suggested that the development of EPS was associated with the duration of peritoneal dialysis, fast peritoneal membrane transport and loss of ultrafiltration. Recently, there have been an increased number of cases of EPS reported in the UK [5]. One of the major differences in clinical practice between the UK and other countries was the introduction of icodextrin-based peritoneal dialysis solutions in the early 1990s. As such, we reviewed our cohort of patients who developed EPS since 2004, with a comparative group of peritoneal dialysis patients who had been treated by peritoneal dialysis for more than 4 years, as recent UK data have suggested a marked increased incidence of EPS after 4 years [9]. Materials and methods Thirty-nine patients had been diagnosed with EPS between January 2000 and April The diagnosis of EPS was based on post-mortem examination or surgical findings at laparotomy consistent with matted smallbowel loops and thickened fibrosed peritoneum (Figure 1) or, in those cases managed medically, clinical presentation with recurrent ascites, obstruction due to small-bowel adhesions and/or thickened calcified perito- Fig. 1. CT scan showing thickened and matted small-bowel loops in a patient with encapsulating peritoneal sclerosis and recurrent ascites detected after transfer to haemodialysis.

3 Encapsulating peritoneal sclerosis 1635 Fig. 2. CT scan showing extensive peritoneal calcification in a patient with encapsulating peritoneal sclerosis. neum on abdominal computerized tomography (CT) scanning (Figure 2). Twenty-six patients (67%) were found to have macroscopic changes compatible with EPS at surgery and/or at post-mortem, and 13 patients suffered episodes in keeping with small-bowel obstruction. Although the median time on peritoneal dialysis in the EPS group was 59 months, eight patients developed EPS within 4 years of starting peritoneal dialysis, with the earliest being after only 9 months of treatment. As duration of peritoneal dialysis treatment has been reported in most studies to be a risk factor for developing EPS, a comparator group of patients who had been treated for more than 4 years was chosen (Table 1). Data were retrospectively collected on clinical factors that have previously been associated with EPS, including patient demographic characteristics, peritoneal dialysis modality, duration of peritoneal dialysis treatment, membrane transport characteristics, peritonitis rates and the outcomes in terms of hospital admissions, morbidity, mortality and survival. This study was performed as an approved internal audit proposed by the clinical governance group, and as such formal informed consent was waived. Biochemical samples were analysed with a standard multi-channel biochemical analyzer (Roche Integra, Roche Diagnostics GmbH, Mannheim, Germany), unless otherwise stated. Dialysate creatinine was measured using a kinetic enzymatic method to prevent glucose interference (P module analyzer, Roche Diagnostics GmbH, Mannheim, Germany). Cancer antigen 125 (CA-125) was measured in peritoneal dialysate effluent drained at the end of a standard peritoneal equilibration test [10] by an electrochemiluminescence ECLIA immunoassay done on the Roche Modular Analytics E170 analyser (Roche Diagnostics GmbH, Mannheim, Germany). Statistical analysis was performed by Student s t-test or Mann Whitney U-test, with Bonferroni correction for multiple analyses where appropriate and by chi-square analysis. Statistical significance was taken as <0.05. Results Thirty-nine patients with EPS were diagnosed between 2000 and To determine the risk of developing EPS, we included all chronic kidney failure patients who had been treated by peritoneal dialysis, who had started treatment at or after the time of our first case in our cohort of EPS patients. During this period, University College London hospitals had treated a total of 1050 patients with peritoneal dialysis, giving an overall prevalence of 3.7%. As the first patient diagnosed with EPS had started treatment prior to 2000, then the overall prevalence is likely to be lower, as patients who had started peritoneal dialysis and either died or transferred modality prior to 2000 were excluded. The incidence of new cases diagnosed with EPS was noted to have increased from only one case in 2000 and 2001 and none in 2002 to five in 2003 then five in 2004, six in 2005, four in 2006, six in 2007 and 11 in Table 1. Patient demographics of the 39 patients diagnosed with encapsulating peritoneal dialysis (EPS) and a comparator control group who had dialysed with peritoneal dialysis for more than 4 years EPS (n = 39) Controls (n = 71) Demographic characteristics Age (year) 56.0* (42 66) 67.0 ( )* Female sex (%) Caucasians (%) Underlying kidney disease Diabetes 10 (25%) 11 (16%) Glomerulonephritis 6 14 Polycystic kidney disease 2 8 Interstitial nephritis 5 5 Others Unknown 4 18 Peritoneal dialysis vintage months 54 ( ) 70 ( ) Peritonitis episodes 1.0 ( ) 1 (0 3.0) Peritoneal dialysis modality CAPD 10 (25.6%) 38 (53.5%)** APD and one day-time exchange 22 (56.4%) 26 (36.6%) APD and two day-time exchanges 7 (17.9%) 7 (9.9%) Dialysate instilled (l/day) 14.2 ± ± 0.5** For those patients returning to peritoneal dialysis following failure of renal transplant, vintage was calculated as time on peritoneal dialysis following failure of transplant. APD, automated peritoneal dialysis cycler; CAPD, continuous ambulatory peritoneal dialysis. Data presented as mean ± SEM, percentage or median (25% quartile). * P < ** P < *** P <

4 1636 A.-M. Habib et al. Table 2. Patient demographics of the 39 patients diagnosed with encapsulating peritoneal dialysis (EPS) and a comparator control group who had dialysed with peritoneal dialysis for more than 4 years EPS (n = 39) Controls (n = 71) Residual renal function Urine output (ml/day) 0 (0 610) 398 (0 1033)* Weekly Kt/V urine 0.25 ± ± 0.1** Adequacy studies Total weekly Kt/V urea 2.24 ± ± 0.10 L creatinine cleared/week 79.4 ± ± 4.5 PD volume (l/day) 14.2 ± ± 0.50*** PD UF (l/day) 0.75 ± ± 0.09 PET studies D/P creatinine 0.84 ± ± 0.02* D/P sodium 0.95 ± ± 0.01 D4/Do glucose 0.30 ± ± 0.01 UF volume (ml) 193 ± ± 21* CA-125 IU/4 h 21.2 ± ± 4.9 Results presented are from the most recent data in those remaining on peritoneal dialysis or last results prior to death on peritoneal dialysis or prior to transfer to haemodialysis and/or transplantation. Dialysis adequacy as total weekly Kt/V urea or litres creatinine cleared/1.73 m 2. Twentyfour-hour volume of peritoneal dialysate used (24-h PD) ultra-filtrate (24-h PD UF) is the difference in volume of peritoneal dialysate effluent drained and that instilled. Data presented as mean ± SEM or median (25 75 % quartiles). PET, Peritoneal equilibrium test [9]; D/P creatinine, ratio of dialysate to plasma concentrations of creatinine; D/P sodium, ratio of dialysate to plasma concentrations of sodium; D4/D0 glucose ratio of initial dialysate to dialysate effluent glucose; UF, PET ultrafiltration volume; CA-125, cancer antigen * P < ** P < *** P < The diagnosis of EPS was made in 50% cases following transfer to haemodialysis, 35% during treatment with peritoneal dialysis, more commonly post peritonitis in 11 of 14 cases, and 15% following transplantation. On followup, 22.5% of the EPS group were subsequently transplanted, compared to 23.9% of the control group, and 55% of the EPS group and 48% of the control group remain alive. Of the control group, 13% currently remain on peritoneal dialysis. Although not statistically different, there were more women in the EPS group than the controls (Table 1). However, overall there were more women treated by peritoneal dialysis, 56% vs 44% in our haemodialysis programmes. The EPS group was younger, with a trend for more patients from the ethnic minorities (Table 1). There were slightly more diabetics in the EPS group, but there were no differences in underlying aetiology of kidney disease. Prior to starting peritoneal dialysis, 35.9% of the EPS group and 9.9% of the controls had previous been transplanted (X 2 =9.4,P = 0.02). There were no differences in the duration of peritoneal dialysis therapy, either excluding previous time spent on peritoneal dialysis prior to transplantation (Table 1) or total time spent on peritoneal dialysis, EPS group 59 ( ) months vs 70 (54 80) months. There were no differences in the number of peritonitis episodes between the groups (Table 1). Of the EPS group, 89.2% had suffered one or more episodes of peritonitis, compared to 73.2% of the control group. More patients in the EPS group were treated by cyclers with additional day-time exchanges than the control group (73.7% vs 46.5% X 2 = 6.86, P = 0.009) and used more peritoneal dialysate per day (Table 2). Glucose concentrations of 22.7 g/l or greater were used by 57.1% of the EPS group and 43.7% of the control group. Both groups used 7.5% icodextrin, 83% of the EPS and 84.5% of the controls; 20% of the EPS group and 28.9% of the controls had received neutral ph dialysates (Physioneal, Baxter Health Care, Deerfield, IL, USA). Urine output and residual renal function were slightly but significantly greater in the control group, but overall adequacy was not different (Table 2). However, daily ultrafiltration volumes tended to be lower in the EPS group, and the most recent peritoneal equilibration test (PET) [10] or that prior to discontinuation of peritoneal dialysis showed that the EPS group tended to be faster transporters with lower ultrafiltration (Table 2). Thirty-eight percent of the EPS group had a PET test net ultrafiltration volume of <100 ml compared to 18% in the control group; P < CA-125 was measured in the peritoneal dialysate effluent at the end of the PET [11] and did not differ between groups: EPS (9.6 ± 1.2 IU/ml) vs controls (14 ± 2.0) or when corrected for drain volumes (Table 2). Angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers had been prescribed to 41.5% of patients in the EPS group and 45.7% of the controls. Similarly, there was difference in prescription of beta blockers between the groups, 38.9% vs 30.9%, respectively. Discussion Encapsulating peritoneal sclerosis remains an uncommon complication of peritoneal dialysis. In our own series, the incidence appears to be increasing. This may either be due to an actual increase in the frequency of EPS or due to increased clinical awareness of the condition and more rapid diagnosis. The difficulty is in determining the denominator, as the risk of developing EPS increases with duration of peritoneal dialysis therapy [3, 4], and as such the risk is reduced for those patients treated for 3 years or less [9]. Even taking a nihilistic approach and assuming that all our patients treated by peritoneal dialysis were at risk of EPS, the annual incidence increased over the last decade from <0.01% to a peak of 1.4%. In half the cases, the diagnosis was only made several months, or in one case more than 2 years, after patients had been transferred to haemodialysis [12]. In just over a third of our cases, EPS developed following a clinical episode of PD peritonitis [4], and 15% were first diagnosed post transplantation, associated with recurrent ascites and/or small-bowel obstruction [13]. As duration of peritoneal dialysis is an accepted risk factor for developing EPS, we compared data between our cohort of EPS patients and a contemporaneous group of patients who had been treated with peritoneal dialysis for a minimum of 4 years, to act as a control group, in keeping with previous reports [14]. Although the two groups had been exposed to peritoneal dialysates for a similar period, the patients in the EPS group were younger, and more patients had been previously transplanted. This was in part due to a number of patients who had been treated with peritoneal dialysis as children, who had then been trans-

5 Encapsulating peritoneal sclerosis 1637 planted and returned to peritoneal dialysis following transplant failure, combined with UK Department of Health initiatives to increase live related transplantation, so resulting in fewer younger patients starting on peritoneal dialysis and so changing the demographics of the peritoneal dialysis population. Although not statistically different, there were more patients in the EPS group from the ethnic minorities, and to some extent this reflects the cosmopolitan nature of inner city London and that waiting times for renal transplantation tend to be longer for those from the ethnic minorities. In our own dialysis programme, more patients from the ethnic minorities are treated by both peritoneal and haemodialysis. Underlying aetiology of kidney failure was not different between the groups. Besides duration of peritoneal dialysis [14], a number of other putative risk factors for developing EPS have been suggested. These include peritonitis episodes, but as with other reports we did not find any increased number of peritonitis episodes in the EPS group [4], although certainly some episodes of EPS were triggered by an episode of peritonitis. Historically, chlorhexidine used as an exit site antiseptic was associated with EPS, and it has been suggested that iodine-based exit site cleansing may have also been a risk factor for EPS [15]. Our local practice was to use topical iodine until 2004 in one centre and then alcohol-based wipes. The other centre used alcohol-based wipes throughout the study period. There was no difference in cases of EPS between centres prior to B-blockers, not only practolol but also timolol and metoprolol, have also been reported to be associated with the development of EPS [4], and others have proposed that angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers may reduce the risk of EPS or help in treatment [16]. However, we found no difference in drug prescriptions between the groups. More patients in the control group stayed on continuous ambulatory peritoneal dialysis (CAPD), whereas more patients in the EPS group had been converted to cycling automated peritoneal dialysis (APD) with one or more day-time exchanges. Typically, the change to cycling PD with a single day-time exchange had occurred relatively early in their time on peritoneal dialysis, whereas the requirements for two day-time exchanges and use of high glucose solutions was much later. Previous smaller studies have suggested that changes in peritoneal transport present even after as little as 1 year of treatment may predict future susceptibility to EPS [14]. Residual renal function was slightly greater in the control group, although overall small solute clearances were similar for both groups. On average, the EPS group achieved a lower net daily peritoneal dialysate ultra-filtrate (UF) volume, despite a slightly increased reliance on hypertonic exchanges [17]. In keeping with this difference in treatment modality, the patients in the EPS group were faster transporters, as defined by the PET D4/P creatinine [10]. Although both groups were predominantly fast transporters, the EPS group had a lower PET ultrafiltration volume, supporting earlier observations [14]. As more EPS patients were treated with cycling machines, the daily exposure to dialysate was greater in the EPS group, although icodextrin and 22.7 g/l or higher glucose-based dialysate usage was similar. Icodextrin was first introduced into our unit in 1995 but was initially restricted, but since 2000, it has been prescribed to the majority of patients, reaching 70% penetration by 2004 and just over 80% in Icodextrin has been shown to be beneficial for peritoneal dialysis patients, by reducing fluid overload compared to hypertonic glucose exchanges [18], and also help stabilize peritoneal membrane function [19]. However, peritoneal function should be monitored by a standardized testing in those patients prescribed icodextrin, rather than simply measuring daily ultrafiltration volumes. Whereas the majority of patients in our centre were once treated by CAPD, the numbers treated by overnight cyclers has steadily increased, and so by 2004 the majority of peritoneal dialysis patients were treated by cyclers, and this has increased to around 67% of the programme. As such this change in dialysis prescription has led to increased exposure to the volume of peritoneal dialysates. The increased exposure to peritoneal dialysates could have also been driven by the introduction of clinical guidelines, both national and international, advocating small solute clearance targets. CA-125 has been reported to reflect peritoneal cell mass and to fall in cases of EPS [20]. However, in our series there was no difference in CA-125 from the PET spent dialysate between those with EPS and the control group. Thus in our series, those patients who developed EPS had increased exposure to peritoneal dialysis solutions in terms of the daily volume prescribed. Standard lactatebased dialysates contain glucose degradation products, including 3,4 dideoxyglucosone-3-ene, 3 deoxyglucosone, aldehydes and formaldehyde. It has been speculated that these chemicals may cause peritoneal membrane injury and increase the risk of developing EPS [21]. However, there is no evidence, as yet, that the use of the newer neutral ph dialysates can prevent EPS. Icodextrin was used widely in both our patient groups, and it has been reported to allow patients with poor ultrafiltration to continue on peritoneal dialysis treatment when otherwise they would be transferred to haemodialysis [22]. Although not all patients were fast transporters, those who developed EPS were faster transporters, with lower PET ultrafiltration volumes. Thus it could be argued that these patients were able to remain on peritoneal dialysis for longer due to the use of icodextrin coupled with changes in peritoneal dialysis prescription, when in retrospect they could have been offered the opportunity to transfer to haemodialysis. However, some eight patients developed EPS within 4 years of starting peritoneal dialysis, and so other factors must be involved in the pathogenesis of EPS rather than simply the duration of therapy and exposure to dialysates. This study would therefore to some extent support suggested clinical guidelines on monitoring PET D/P creatinine ratios and considering modality transfer to those patients with increasing D/P creatinine ratios in association with reduced ultrafiltration volumes, requiring exposure to higher glucose solutions [23]. However, the majority of our cases with EPS were only diagnosed after transfer to haemodialysis, as even in retrospect only a minority of patients had symptoms or clinical signs suggestive of EPS whilst on peritoneal dialysis. Thus, whether elective trans-

6 1638 A.-M. Habib et al. fer from peritoneal to haemodialysis would hasten or delay the onset of EPS remains unknown. Acknowledgements. Easter Dr Preston tragically died in a skiing accident, Conflict of interest statement. None declared. References 1. Davenport A. Peritonitis remains the major clinical complication of peritoneal dialysis: the London, UK, peritonitis audit Perit Dial Int 2009; 29: Gandhi VC, Humayan HM, Ing TS. Sclerotic thickening of the peritoneal membrane in maintenance peritoneal dialysis patients. Arch Intern Med 1980; 140: Kawanishi H, Kawaguchi Y, Fukui H et al. Encapsulating peritoneal sclerosis in Japan: a prospective controlled, multicenter study. Am J Kidney Dis 2004; 44: Rigby RJ, Hawley CM. Sclerosing peritonitis: the experience in Australia. Nephrol Dial Transplant 1998; 13: Balasubramaniam G, Brown EA, Davenport A et al. The Pan-Thames EPS study: treatment and outcomes of encapsulating peritoneal sclerosis. Nephrol Dial Transplant Yamamoto R, Nakayama M, Hasegawa T et al. High-transport membrane is a risk factor for encapsulating peritoneal sclerosis developing after long-term continuous ambulatory peritoneal dialysis treatment. Adv Perit Dial 2002; 18: Oules R, Challah S, Brunner FP. Case-control study to determine the cause of sclerosing peritoneal disease. Nephrol Dial Transplant 1988; 3: Nomoto Y, Kawaguchi Y, Kubo H et al. Sclerosing encapsulating peritonitis in patients undergoing continuous ambulatory peritoneal dialysis: a report of the Japanese Sclerosing Encapsulating Peritonitis Study Group. Am J Kidney Disease 1996; 28: Brown MC, Simpson K, Kerssens JJ et al. Encapsulating peritoneal sclerosis in the new millennium: a national cohort study. Clin J Am Soc Nephrol 2009; 4: Twardowski ZJ, Nolph KD, Khanna R et al. Peritoneal equilibrium test. Perit Dial Bull 1987; 7: Willicombe MK, Davenport A. Hydration status does not influence peritoneal equilibration test ultrafiltration volumes. Clin J Am Soc Nephrol 2009; 4: Kawanishi H, Moriishi M. Epidemiology of encapsulating peritoneal sclerosis in Japan. Perit Dial Int 2005; 25: S14 S Korte MR, Yo M, Betjes MG et al. Increasing incidence of severe encapsulating peritoneal sclerosis after kidney transplantation. Nephrol Dial Transplant 2007; 22: Hendriks PM, Ho-dac-Pannekeet MM, van Gulik TM et al. Peritoneal sclerosis in chronic peritoneal dialysis patients: analysis of clinical presentation, risk factors, and peritoneal transport kinetics. Perit Dial Int 1997; 17: Lo WK, Chan KT, Leung AC et al. Sclerosing peritonitis complicating continuous ambulatory peritoneal dialysis with the use of chlorhexidine in alcohol. Adv Perit Dial 1990; 6: Miyazaki M, Yuzawa Y. The role of peritoneal fibrosis in encapsulating peritoneal sclerosis. Perit Dial Int 2005; 25: S48 S Yamamoto R, Otsuka Y, Nakayama M et al. Risk factors for encapsulating peritoneal sclerosis in patients who have experienced peritoneal dialysis treatment. Clin Exp Nephrol 2005; 92: Davies SJ, Woodrow G, Donovan K et al. Icodextrin improves the fluid status of peritoneal dialysis patients: results of a double-blind randomized controlled trial. J Am Soc Nephrol 2003; 14: Davies SJ, Brown EA, Frandsen NE et al. Longitudinal membrane function in functionally anuric patients treated with APD: data from EAPOS on the effects of glucose and icodextrin prescription. Kidney Int 2005; 67: Ho-dac-Pannekeet MM, Hiralall JK, Struijk DG et al. Longitudinal follow-up of CA125 in peritoneal effluent. Kidney Int 1997; 51: Davies SJ, Phillips L, Naish PF et al. Peritoneal glucose exposure and changes in membrane solute transport with time on peritoneal dialysis. J Am Soc Nephrol 2001; 12: Wilkie ME, Plant MJ, Edwards L et al. Icodextrin 7.5% dialysate solution (glucose polymer) in patients with ultrafiltration failure: extension of CAPD technique survival. Perit Dial Int 1997; 17: Kawaguchi Y, Saito A, Kawanishi H et al. Recommendations on the management of encapsulating peritoneal sclerosis in Japan, 2005: diagnosis, predictive markers, treatment, and preventive measures. Perit Dial Int 2005; 25: S83 S95 Received for publication: ; Accepted in revised form: