Dialysis used successfully in the past.6 Taken together, a trial of corticosteroids


should be administered fairly quickly in most patients who fail to respond to conservative therapies after peritonitis or other intra-abdominal infections have been ruled out.


Case series describing the use of tamoxifen (a non-steroidal, anti-estrogenic drug with antifibrotic properties) alone or in combination with corticosteroids have demonstrated it to have some efficacy in the management of EPS.41,44–47


This in turn prevents fibrosis of the membrane. While tamoxifen therapy is generally well tolerated as it is devoid of the catabolic and immunosuppressive effects of corticosteroids, it does have serious side effects, most notably increased thromboembolic risk. Historically, tamoxifen has been used during the progressive and fibrotic stages of EPS in order to minimize ongoing fibrosis. Obviously, further trials are needed in order to clearly define the role of this potentially important therapy.


the peritoneal membrane by downregulating the expression of TGF-β by fibroblasts.45


While nutritional support is crucial at all stages of EPS, it is of paramount importance during the late stages of EPS when gastrointestinal symptoms become pervasive and malnutrition may set in. At this point, enhancement of nutritional support using total parenteral nutrition (TPN) is usually necessary. The evidence for the role of TPN in the management of EPS remains equivocal, with some studies demonstrating benefit and others showing harm.6,7


Nevertheless, taken


at face value, TPN may play a key role in the prevention and treatment of malnutrition in patients with EPS.


Despite the use of TPN, tamoxifen, and corticosteroids in the management of EPS, approximately 50% of patients do not respond and eventually require surgery.48


Surgical therapy includes lysis of intestinal


Numerous studies have proved enterolysis to be safe and effective when performed in an experienced center, with mortality rates less than 4%.42,48,49


adhesions, a process known as enterolysis, as well as stripping of the fibrous cocoon.48


Accepted indications for surgery in EPS


include persistent bowel obstruction, failing nutritional status, failure to respond to conventional therapy, and recurrent episodes of peritonitis secondary to bowel compromise.50


It is important that surgical


intervention be sought prior to the appearance of malnutrition, which may increase post-operative morbidity and mortality.


While surgery reverses intestinal obstruction, recurrence of symptoms occurs in up to 25% of patients, usually within 12–24 months.42


Modified


surgical techniques, such as Noble plication, during which the small bowel walls are stitched together to prevent the formation of post- operative adhesions, in combination with enterolysis have yielded dramatic reductions in recurrent symptoms.51


Immunosuppressive agents such as azathioprine or mycophenolate mofetil (MMF) combined with prednisolone have been used in the past to treat EPS and have demonstrated efficacy.17,43,52


New therapies


using blockers of the renin–angiotensin system (RAS) and antifibrotic agents such as everolimus have shown benefit in animal models.53–56 Further evaluation of these agents is necessary in order to draw definite conclusions.


74


Renal Transplantation and Encapsulating Peritoneal Sclerosis


Two Dutch units recently demonstrated an increase in the number of cases of EPS occurring after renal transplantation.57,58


In contrast to the It is believed to impart its beneficial effect on


typical presentation of EPS, these cases presented with fulminant intestinal obstruction shortly after transplantation. Such acute onset of EPS symptoms was further corroborated by de Frietas et al., who reported 23 cases of EPS occurring within one year after renal transplant in patients previously on PD.59


Both termination of PD and


transplantation-related factors can be invoked to explain the phenomenon of post-transplantation EPS.60,61


The discontinuation of


the ‘wash-out effect’ of PD leads to an increase in concentrations of fibrin and pro-inflammatory mediators, which can give rise to and propagate EPS. This is combined with the profibrotic effects of certain immunosuppressant medications used in renal transplantation, most notably the calcineurin inhibitors (CNIs).62,63


Animal data suggest that


CNIs in conjunction with ongoing PD may propagate the profibrotic and inflammatory processes occurring in the peritoneal membrane.63 Moreover, the trend toward the use of steroid-sparing protocols may remove the attenuating role of corticosteroids on inflammatory responses in the peritoneal membrane.60


Prevention of Encapsulating Peritoneal Sclerosis Despite improvements in the treatment of EPS, an effective management strategy that restores peritoneal integrity remains elusive. In this regard, prevention of EPS is of paramount importance. The most rational approach to prevent EPS is to implement practices that address its risk factors. Although there is a paucity of evidence for strategies aimed at preventing EPS, emphasis has been placed on practices such as effective peritonitis prevention and management, the use of ‘biocompatible’ dialysis solutions and the avoidance of pre-emptive discontinuation of PD with transfer to hemodialysis (HD).64–66


As


previously mentioned, the incidence of EPS increases with time on PD, particularly after five years of treatment.14


However, the majority of


long-term PD patients do not develop EPS, and the practice of pre-emptive discontinuation of PD with transfer to HD did not demonstrate any merit in a prospective study.6


In fact, this practice may


unintentionally act as a stimulus for the development of EPS. Therefore, pre-emptive transfer to HD should only be considered in patients with a very high risk for EPS.14


Such features include a high and rising


peritoneal permeability, low ultrafiltration capacity, frequent episodes of peritonitis, and requirement for high glucose concentration dialysate.14 Obviously, close follow-up would be warranted as EPS can develop many years after discontinuation of PD. Other strategies that have been suggested to prevent EPS include antifibrotic medications and peritoneal lavage.65,66


These approaches lack high-level supportive


evidence and have thus been abandoned as prophylactic measures. Conclusion


Despite advances in our understanding of EPS over the past two decades, limitations in our knowledge of its detection, pathophysiology, and treatment still exist. Ultimately, the way to advance our understanding of this condition is through a multinational collaborative research approach. Such partnership will allow for improvements in the diagnosis of EPS and identification of candidate genes, and create a platform for novel treatment strategies to be trialled. n


US NEPHROLOGY


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