NDT Advance Access originally published online on March 29, 2007
Nephrology Dialysis Transplantation 2007 22(8):2412-2414; doi:10.1093/ndt/gfm171
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Increasing incidence of severe encapsulating peritoneal sclerosis after kidney transplantation
Correspondence and offprint requests to: Email: m.korte{at}erasmusmc.nlSir,
Encapsulating peritoneal sclerosis (EPS) is a life-threatening complication of peritoneal dialysis (PD). Since the first report in 1980 [1], the reported overall prevalence of EPS has varied between 0.7% in Australia [2], 2.5% in Japan [3] and 3.3% in a single-centre study in Great Britain [4]. The diagnosis of EPS is difficult, mainly because a uniformly used definition is lacking. Most clinicians use the criteria defined by the Ad Hoc Committee of the International Society of Peritoneal Dialysis (ISPD) [5]. This committee defined EPS as: ‘A clinical syndrome with persistent, intermittent or recurrent presence of intestinal obstruction with or without the existence of inflammation parameters and the existence of peritoneal thickening, sclerosis, calcifications and encapsulation confirmed by macroscopic inspection or radiological findings’. It is our distinct impression that in recent years we are witnessing a marked increase in the incidence of EPS. In order to investigate whether this suspicion is justified, we initiated an analysis of the occurrence of EPS in two university hospitals in The Netherlands (Erasmus Medical University Centre in Rotterdam and the Utrecht Medical Centre in Utrecht). Both centres serve as regional transplantation centres and are comparable in patient population. Cases were identified by retrospective investigation of the medical records of both PD populations in the period 1998–2005. Patients at risk for developing EPS were defined as either having previous PD treatment or patients with a history of PD having undergone renal transplantation no more than 3 years ago. Encapsulating peritoneal sclerosis was defined according the criteria developed by the ISPD [5].
Eighteen cases (13 males/five females, age 39.8 ± 10.2 years) of severe EPS were identified. Twelve of these patients were treated at the Erasmus Medical Centre and six patients at the Utrecht Medical Centre. Thirteen patients were not on PD at the time of diagnosis and were either on haemodialysis or had received a functioning kidney graft.
The PD population, treated in the period 1998–2005, comprised of 418 patients (206 patients in Rotterdam and 212 in Utrecht). In both 1998 and 1999, there was one EPS case each year, in 2002 one case and in 2003 two cases. However, in 2004 and 2005 we observed three and 10, cases respectively. The number of patients on PD did not change significantly in time throughout the whole period in both the centres. Although there was a steady increase in patients alive with functioning kidney graft and a history of PD, the increasing incidence of EPS exceeded the increase in patients at risk (Figure 1, P = 0.038, using a Pearson's chi-square test for trend analysis).
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Patients had a mean time on PD of 71.8 ± 44.9 months at the time of EPS diagnosis. Seventeen patients used icodextrin and the mean time on icodextrin was 34.2 ± 22.2 months. Seven patients were treated with icodextrin within the period between November 2001 and July 2002, when an outbreak of icodextrin-associated peritonitis occurred [6]. In these patients, there was no history of aseptic peritonitis.
Fifteen patients (83%) had a history of kidney transplantation. The mean time from the last kidney transplantation to the diagnosis of EPS diagnosis was 39.3 ± 71.1 months.
The overall mortality was 50%. In eight patients death was attributable to EPS.
This study shows that in two Dutch university hospitals the incidence of severe EPS has increased significantly in the period from 1998 to 2005 in stabile PD populations. Earlier reports also appeared to indicate an increased incidence of EPS [2,7]. In these retrospective surveys the apparent increase was related to the duration of PD treatment, with substantial increased prevalence after 5 years of PD [2]. However, in our study the majority of patients were on PD for a considerably shorter period than 5 years when they developed EPS.
The pathophysiology of EPS is unknown, but it appears that EPS is not solely the result of progression of peritoneal remodelling that happens with PD. A second hit, has been postulated to aggravate the damage to the peritoneum and to induce the further development of EPS [8]. Although limited by the retrospective nature of this study, we investigated whether infection [2] or type of dialysis solution [9–11] could be such a second hit.
However, the mean number of peritonitis episodes was only 0.54 ± 0.73 for every year of PD and we found no increase of specific micro-organisms in the EPS population. Almost all of the patients developing EPS used icodextrin. Since half of our patients were treated with icodextrin during the period in which the outbreak with icodextrin-related aseptic peritonitis [12,13] occurred, a possible contribution of icodextrin to the development of EPS cannot be entirely excluded and has to be evaluated.
As the majority of EPS patients underwent a kidney transplantation at some point in time, transplantation, with subsequent immunosuppressive treatment, could also be considered as the second hit in the development of EPS. This suggestion is strengthened by the fact that, in some patients, EPS developed shortly after kidney transplantation. It remains unclear whether the transplantation procedure itself or the concomitant medication is responsible. Cessation of peritoneal lavage after transplantation could lead to diminished clearance of fibrin and may thus contribute to peritoneal fibrosing. Also, the known profibrotic effects of calcineurin inhibitors (CNIs) may have had an effect on the development of EPS [14,15].
In conclusion, this study confirms our impression that the incidence of EPS has increased in the last few years. The design of this study precludes conclusions on the cause of the increased incidence, but the remarkable preponderance of EPS patients with a functioning renal allograft may point towards a pathogenetic role of kidney transplantation. A multicentre study is urgently needed to address this increasing threat to the patients on PD.
1Erasmus Medical University
Centre, Rotterdam
2Utrecht Medical University Centre
Utrecht, The Netherlands
Acknowledgement
We are grateful to Dr W.C. Hop from the Department of Medical Statistics of the Erasmus Medical Centre for his expert advice on the statistical analysis.
Conflict of interest statement. None declared.
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