Peritoneal Sclerosis — An Overview

Guido Garosi and Nicola Di Paolo

The term peritoneal sclerosis encompasses a vast range of peritoneal alterations, from the low clinical impact manifestations associated with chronic peritoneal dialysis, to dramatic thickening of the peritoneal membrane, which is rare, but often life-threatening. The frequency, pathology, etiopathogenesis, clinical manifestations, diagnostic criteria, therapy, and prevention of peritoneal sclerosis are reviewed. Preliminary observations from the Italian Registry of Peritoneal Sclerosis, established in the framework of a program of the Italian Society of Nephrology, are reported.

Key words

Biocompatibility, peritoneal sclerosis, peritonitis, sclerosing peritonitis

From:

Nephrology and Dialysis Department, Le Scotte Hospital, Siena, Italy.

Introduction


The term peritoneal sclerosis (PS) can be applied to a vast range of peritoneal alterations. At one end is simple sclerosis (SS), the slight peritoneal sclerosis associated with chronic peritoneal dialysis (PD). At the other end is sclerosing peritonitis (SP), which is rare, but which involves dramatic peritoneal thickening.

Sclerosing peritonitis is widely interpreted (1-6) as an unfavorable evolution of SS. However, research has been concentrated on the two extremes of the spectrum (1-6), with little data on what should be the intermediate stages. This situation casts doubt on whether SP can in all cases be attributed to evolution of SS, and, in fact, SP sometimes seems to be a separate entity.

Frequency


Simple sclerosis is extremely frequent. Rubin's group (7) found some initial aspects of fibrosis in all 16 PD patients examined, although the thickness of the submesothelial fibrotic tissue was usually less than 20 m. Schneble's group (8) found initial aspects of fibrosis associated with PD in 50% of cases after only 6 - 12 months of dialysis. In the experience of our group (3), about 80% of patients have signs of SS after 2 years of PD.

Sclerosing peritonitis, on the other hand, is rare. Three recent well-documented studies (4-6) estimate a prevalence of 0.5% - 0.9% in PD patients and an incidence of between 0 and 4.3 per thousand patient-years. In Italy, we have started to collect data for a program of the Italian Society of Nephrology. So far, we have recorded 16 cases, for an incidence of 3.9 cases per thousand patient-years.

Pathology


Simple sclerosis


The classical descriptions of peritoneal alterations associated with PD (1-3) begin with mesothelial modifications and later extend to submesothelial alterations and SS. Mesothelial modifications include ultrastructural alterations, cuboidal transformation, and loss of mesothelium. Histological alterations include thickening and reduplication of the basement membrane of mesothelium and blood vessels, a variable degree of submesothelial edema, and a modest increase in cell elements. In this context, SS is practically a constant finding (Figure 1): it consists of sclerotic tissue that rarely extends to the whole peritoneum, but is limited to visceral and parietal areas. The thickness of the sclerotic submesothelial tissue does not exceed 40 m.

Sclerosing peritonitis


Unlike SS, SP (1-3) is characterized by dramatically progressive sclerosis combined with aspects such as inflammatory infiltrates, calcification, and typical vascular alterations. These features cast doubt on a necessary link between SS and SP.

Macroscopically, the peritoneal surface (1-3) is reduced to a rough thickened membrane similar to the sole of a shoe, causing rigidity and thickening of the intestinal loops. In sclerosing encapsulating peritonitis, the sclerotic process completely fixes groups of intestinal loops, almost completely preventing their movement. Any abdominal organ may be involved in sclerosis. Often the sclerosis is not of the same degree throughout the abdomen: one area may be more affected than others, forming a mass. This situation has been described with the term "abdominal cocoon."

Figure 1: Simple sclerosis. Thin submesothelial sclerotic tissue. Hematoxylin-eosin, ×100.
Figure 2: Sclerosing peritonitis. Thick submesothelial sclerotic tissue. Hematoxylin-eosin, ×40.

The microscopic picture is dominated by sclerosis (1-3), with compact sclerotic tissue consisting of dozens of irregular layers (Figure 2). In the matrix, fibroblasts and mesoblasts are prevalent. The thickness of the sclerotic tissue is not uniform in a given patient, but reaches very high values, up to 4000 m. The thickness is always well beyond the 40 m proposed as the upper limit in SS. Our experience confirms that the thickness of the sclerotic tissue is the best pathological criterion for differential diagnosis of the two conditions.

In many cases of SP (1-3), cellular infiltrate is found in the sclerotic tissue, containing leukocytes, erythrocytes, isolated macrophages, and giant cells (Figure 3). Areas of genuine parvicellular infiltration may be observed, and these may organize into micro-abscesses. Sometimes granulation tissue is observed. These signs of inflammation are not constant. In the 16 patients that constitute our experience, we found parvicellular infiltration in 5 cases, micro-abscesses in 2 cases, and giant cells in 4 cases. These aspects of chronic inflammation pose certain questions. We can ask whether pictures of this type may persist after clinical recovery from peritonitis in PD patients, as suggested by Boroujerdi-Rad's finding (9) that small abscesses complicate 0.7% of cases of peritonitis in PD. The existence of significant chronic inflammation in a proportion of patients with SP raises the next question, that of antibiotic treatment.

Peritoneal calcifications (1-3) are almost always found in SP. They are associated with sclerotic tissue in concentric layers, and may demonstrate the presence of inflammatory infiltrates. These characteristics qualify them as dystrophic calcifications. Sometimes, ossification of the peritoneum has been observed. In a young patient, age 20 years, we observed tissue with the characteristics of bone marrow inside islands of ossification (Figure 4). As far as we know, this is the first observation of bone marrow in the peritoneum.

Figure 3: Sclerosing peritonitis. Giant cells of macrophagic origin are detected in sclerotic tissue. These cells indicate chronic inflammation. Parvicellular infiltration is also present. Hematoxylin-eosin, ×250.
Figure 4: Sclerosing peritonitis. Area of bone marrow inside an island of ossification. Hematoxylin-eosin, ×250.

Vascular alterations in SP (1-3) are not limited to thickening and replication of the basement membrane as described for SS, but often include accentuated sclerosis of the tunica media (Figure 5). Quite large vessels may become occluded.

The latest topic in the pathology of SP is giant mesothelial cells. Yamamoto's group (10) recently found many giant mesothelial cells in patients with SP. This finding is not in line with our results and requires confirmation (11). It is surprising to find so many giant mesothelial cells in patients with SP who have almost complete loss of mesothelium.

Etiology and pathogenesis


Duration of dialysis


Because SS (3,7-8) is extremely frequent in early dialysis, PD can probably be regarded as an etiologic factor rather than a risk factor.

The situation for SP is quite different. Well-documented epidemiological studies (4-6) report a constant link between duration of PD and incidence of SP. Exceptions, however, are not lacking, showing that no link is necessary between duration of PD and development of SP. Curiously, SP sometimes does not manifest until long after suspension of PD.

Poor biocompatibility


Figure 5: Sclerosing peritonitis. Complex vascular alterations, with reduplication of the basement membrane and sclerosis of the tunica media. Hematoxylin-eosin, ×100.

Substantial agreement exists (12-13) that the poor biocompatibility of PD — mainly due to osmotic agents, hyperosmolarity, low pH, and buffer systems — is the main reason why anatomical alterations of the peritoneum are a constant in PD. Simple sclerosis could be a direct effect of poor biocompatibility. Reduced production of phospholipids by mesothelial cells, the strong effects on complex mesothelial cytokine secretion, and the repercussions on the biology of leukocytes, especially macrophages and fibroblasts, provide biochemical documentation of the functional and morphological changes always associated with PD, including SS. The morphological changes associated with PD have also been reproduced in animal models (14-15). We can therefore say that the poor biocompatibility of current PD solutions causes chronic irritation of the peritoneum. Simple sclerosis is a morphological component of chronic irritation.

Although the poor biocompatibility of PD is an obvious risk factor for SP, it is not always possible to identify the factor that triggers the transformation from SS to SP. Epidemiological studies (4-6) have pinpointed this factor in some cases, but in others the cause remains unknown. In vitro models (12-13) have explained the biochemical basis of the correlation between poor biocompatibility and SS, but they have been less convincing in reproducing the link with SP. Animal models failed to realistically reproduce SP (14-15).

The transformation of SS to SP has been ascribed to several factors correlated with poor biocompatibility: acetate buffer, chlorhexidine, povidone iodine, catheters, in-line bacterial filters, particles of plastics, and plasticizers.

Sclerosing peritonitis was found (16) to occur at a higher frequency with acetate buffer than with lactate buffer. This finding led to discontinuation of acetate buffer throughout the world. Studies with liver cells (17) showed that high local concentrations of acetate were associated with gross impairment of cell function.

The use of solutions of chlorhexidine in alcohol to sterilize the connections for PD has been epidemiologically associated with the development of SP (4-6). Experimental studies with rats (18) have revealed that this type of disinfectant reaches the peritoneum and causes striking pathological changes in mesothelium, submesothelial stroma, and underlying muscle.

Povidone iodine is another antiseptic used in PD and implicated in the development of SP. Significant epidemiological correlations (19) contraindicate this disinfectant for PD patients.

The presence of the peritoneal catheter has been regarded as a risk factor for SP (4-6). The catheter can indeed cause (20) a foreign-body response with chronic inflammation. Alterations similar to SP have been documented in patients with ventriculoperitoneal shunt and Le Veen shunt (21). It has been suggested that the risk factor may not be the catheter, but its surgical insertion (22). A higher frequency of previous abdominal surgery in patients with SP has been reported (22).

In-line bacterial filters have been associated with an increased frequency of SP, though authors are not unanimous on this point (4-6). Bacteria trapped in the filters (23) may secrete pyrogens that enter the peritoneal cavity and stimulate macrophage secretion of interleukin-1 (IL-1).

Bags and tubes for dialysis are known (24) to release particles of plastics that may cause reactive fibrosis in the peritoneum, probably by an immune-mediated mechanism.

Plasticizers are soluble compounds released by bags and tubes. There is experimental evidence that they induce IL-1 secretion by mononuclear cells (25).

To sum up the link between poor biocompatibility of PD and peritoneal sclerosis, poor biocompatibility can certainly produce chronic irritation, which is the basis for the morphological changes associated with chronic PD, including SS. This chronic inflammatory state is also a risk factor for SP. Various factors linked to biocompatibility explain the transformation from SS to SP in some cases; however, in most cases, poor biocompatibility alone does not explain SP development.

Peritonitis


Peritonitis is the most commonly invoked pathogenetic factor for SP (4-6). This hypothesis is supported by significant epidemiological data (4-6). However, peritonitis is not an obligatory factor: SP can be demonstrated in patients who never experienced peritonitis (4,6). Certain etiological agents are also recognized to be more dangerous than others (4-6), especially Staphylococcus aureus, fungi, Pseudomonas species, and Haemophilus influenzae.

Figure 6: Just after peritonitis, clusters of fibrin penetrate the submesothelial tissue. Hematoxylin-eosin, ×40.

The pathogenetic mechanisms by which peritonitis promotes evolution to SP are well known (26,27). The starting point is loss of mesothelium during peritonitis. This loss facilitates damage by any bioincompatible substance in PD solutions, and above all causes loss of fibrinolytic capacity. Mesothelial cells have high fibrinolytic capacity and play an essential role in keeping the balance between production and reabsorption of fibrin on the breakdown side of the equation. During peritonitis, bacterial infections stimulate fibrin production, while peritoneal fibrinolytic capacity decreases owing to loss of mesothelium. If the noxa is quickly removed and the mesothelium survives or regenerates in a reasonably short time, the fibrinolytic capacity of the mesothelium controls the process and no evolution towards fibrosis occurs. If, on the other hand, the fibrinolytic capacity of the mesothelium is compromised for too long, the balance shifts towards fibrin production and organization on a large scale (Figure 6), which is determinant for SP.

Related to the problem of peritonitis, we have the observation that certain antibiotics administered intraperitoneally may cause chemical peritonitis (5), thus favoring the development of SP. The antibiotics suspected include vancomycin, cephalothin, cefuroxime, tobramycin, sulfamethoxazole, and amphotericin B. Quick and complete control of the infection is nevertheless imperative.

Peritoneal dialysis-independent sclerosing peritonitis


Because not all cases of SP in PD patients are explained by PD-related factors, it is important to consider SP in non dialytic patients.

Practolol and other beta-blockers, such as atenolol, metoprolol, propranolol, oxprenolol, and timolol were associated with idiopathic SP (28). However, in PD patients, epidemiological studies (4-6) have not been able to find a statistically significant relation between beta-blockers and SP. Recent studies by Stegmayr (29) and Krediet (30) show that beta-blockers induce a decrease in ultrafiltration, irrespective of SP. All of these observations mean that beta-blockers are contraindicated in PD patients.

Sclerosing peritonitis has often been reported as a paramalignant phenomenon (31) in association with gastric cancer, ovarian thecoma, ovarian teratoma, carcinoma of the pancreas, multiple polyposis, histiocytic lymphoma, and renal carcinoma.

In many cases of SP (32), no correlation can be established with any causal factor. From our point of view, two factors are important. The first is that in these forms, peritoneal impairment is often associated with retroperitoneal or mediastinal fibrosis, mesenteric adipose necrosis, pericardial or pleural sclerosis, or dry keratoconjunctivitis. In many cases, there seems to be connective tissue impairment in general, particularly of the serous membranes. The second factor may be genetic predisposition, evidence in favor of which includes the high frequency of SP in women from subtropical areas (32) and familial forms, such as familial multifocal fibrosclerosis described in 1967 by the Comings group (33).

Summing up, the etiopathogenesis of SP is considered to be multifactorial: any irritant of the peritoneum predisposes to this syndrome. Sclerosing peritonitis can broadly be traced to various aspects of poor biocompatibility of PD, to peritonitis, and perhaps to other causes such as beta-blockers. However, only a small proportion of patients subject to these stimuli develop SP. Genetic predisposition, if it exists, may be the basic trigger for the development of SP.

Clinical manifestations


SS has no clinical manifestations (3,7,8).

With regard to SP, loss of peritoneal dialytic efficiency is the first point to discuss. According to Krediet (34), SP is associated with a deficit in dialytic capacity. This deficit makes it possible to identify subjects at risk by monitoring peritoneal solute and fluid kinetics. However, several cases of SP with no apparent changes in peritoneal dialytic capacity have been reported (4-6). In our population, 13 of 16 cases showed a deficit in solute or fluid removal before diagnosis; the other 3 did not. It is difficult to conceive of normal solute or fluid removal with the severe anatomical changes observed in SP, but apparently it does occur.

The list of symptoms associated with SP (4-6) include anorexia, nausea, vomiting, diarrhea, constipation, abdominal distension, fever, weight loss, abdominal pain, palpable abdominal mass, incomplete or complete bowel obstruction, hemorrhagic effluent, and ascites. Onset is often insidious, with vague bowel symptoms. In other cases, onset may be acute, manifesting directly as bowel obstruction.

Diagnosis of sclerosing peritonitis


Plain x-ray and contrast studies (4-6) may be completely negative, even in cases of severe SP. Signs suggesting SP include dilated small bowel loops with gas-fluid levels, calcifications in the peritoneum and intestinal wall, and, sometimes, bowel wall thickening. In contrast studies, signs suggesting SP are motility disturbances with delayed transit, varying degrees of obstruction accompanied by hypermobility of some loops, and separation of small bowel loops that appear fixed and rigid.

Ultrasound studies (4-6) are more specific: besides the usual signs of obstruction and loculated ascites, there is often typical thickening of the intestinal wall. Computed tomography (4-6) is more accurate, providing more detail of obstruction, loculated ascites, calcifications, and thickening of the peritoneum.

Although histological examination is an invasive method, in our opinion a reliable diagnosis can be obtained by measuring the thickness of the sclerosis. The degree of inflammation can then be verified, which is useful for deciding antibiotic therapy.

Therapy


Surgery is usually reserved for intestinal occlusion (4-6). The elective method is membrane resection; otherwise, enterolysis with partial excision of the membrane, or intestinal resection can be undertaken. The extremely high mortality, about 60%, is due to post-operative complications, typically opening of intestinal anastomoses.

Interruption of PD and catheter removal are generally advocated (4-6), and these measures are, in most cases, accompanied by considerable improvement in symptoms and some regression of the anatomical lesions, probably due to removal of this non physiological stimulus.

In the last ten years, many cases of SP have been treated with steroids and immunosuppressants (4-6). Steroids have been used alone, or with cyclophosphamide, azathioprine, or colchicine. This type of therapy arose from the observation that SP was well controlled in many patients undergoing kidney transplant and immunosuppression, although in others it continued to evolve.

Other therapies described in the literature (4-6) include total parenteral nutrition, intraperitoneal administration of phosphatidylcholine, progesterone, and tamoxifen.

Signs of chronic infection in some SP patients raised the question of antibiotic therapy, at least in cases with histological evidence of chronic inflammation. In our cases, before suspending PD and removing the catheter, we give a cycle of intraperitoneal antibiotics, as if we were treating peritonitis. We choose the drug and the protocol on the basis of the etiological agent of the last episode of peritonitis. Later, we remove the catheter and the patient transfers to hemodialysis and is treated with steroids and cyclophosphamide, followed by steroids and azathioprine. This protocol has been adopted by the PD Study Group of the Italian Society of Nephrology, which has created a national register for SP. It is still early to judge, but we hope that this approach will be successful, at least in some cases. The high mortality of SP (20% - 93%) (4-6) justifies strong therapy.

Prevention


Poor prognosis makes SP prevention very important (4-6). The advised measures include use of more biocompatible PD solutions, avoidance of intraperitoneal drugs (except antibiotics), careful management of peritonitis, periodic evaluation for peritoneal transport and ultrafiltration, regular radiologic and sonographic screening. High transforming growth factor b1 (TGFb1) levels in dialysate were proposed as a parameter for predicting SP. We suggest performing a peritoneal biopsy at any peritoneal catheter insertion or removal, and withdrawal from PD if a sclerosis > 40 m thick is demonstrated. In experimental studies with rats, intraperitoneal administration of octreotide (35), a somatostatin analogue used to inhibit release of growth hormone, or glycosaminoglycans (36) was found to have a protective effect.

Conclusions


Simple sclerosis is regularly encountered after months or years of PD and is directly related to poor biocompatibility of PD solutions. It may contribute to the progressive long-term loss of efficiency of PD, though its clinical impact is low.

Sclerosing peritonitis, on the other hand, is very rare. Its pathology only partly suggests that it evolves from SS, many aspects indicating that it may be a separate nosological entity. Sometimes the factors triggering it can be identified, especially with regard to episodes of peritonitis and various aspects of poor biocompatibility of PD. However, in many cases, the triggering factor cannot be identified. Therapy for SP should be aggressive, including suspension of PD, catheter removal, and steroid and immunosuppressant therapy, possibly preceded by cycles of antibiotics.

References


  1. Dobbie JW. Morphology of the peritoneum in CAPD. Blood Purif 1989; 7:74-85.
  2. Gotloib L, Shostak A. Peritoneal ultrastructure. In: Nolph KD, ed. Peritoneal dialysis. 3rd edition. Dordrecht: Kluwer Academic Publishers, 1989: 67-95.
  3. Di Paolo N, Sacchi G. Anatomy and physiology of the peritoneal membrane. Contrib Nephrol 1990; 84:10-26.
  4. Nomoto Y, Kawaguchi Y, Kubo H, Hirano H, Sakai S, Kurokawa K. Sclerosing encapsulating peritonitis in patients undergoing continuous ambulatory peritoneal dialysis: A report of the Japanese Sclerosing Encapsulating Peritonitis Study Group. Am J Kidney Dis 1996; 28:420-7.
  5. Afthentopoulos IE, Passadakis P, Oreopoulos DG. Sclerosing peritonitis in continuous ambulatory peritoneal dialysis patients: One center's experience and review of the literature. Adv Ren Replace Ther 1998; 5:157-67.
  6. Rigby RJ, Hawley CM. Sclerosing peritonitis: The experience in Australia. Nephrol Dial Transplant 1998; 13:154-9.
  7. Rubin J, Herrera GA, Collins D. An autopsy study of the peritoneal cavity from patients on continuous ambulatory peritoneal dialysis. Am J Kidney Dis 1991; 18:97-102.
  8. Schneble F, Bonzel KE, Waldherr R, Bachmann S, Roth H, Scharer K. Peritoneal morphology in children treated by continuous ambulatory peritoneal dialysis. Pediatr Nephrol 1992; 6:542-6.
  9. Boroujerdi-Rad H, Juergensen P, Mansourian V, Kliger AS, Finkelstein FO. Abdominal abscesses complicating peritonitis in continuous ambulatory peritoneal dialysis. Am J Kidney Dis 1994; 23:717-21.
  10. Yamamoto T, Izumotani T, Otoshi T, Kim T. Morphological studies of mesothelial cells in CAPD effluent and their clinical significance. Am J Kidney Dis 1998; 32:946-52.
  11. Di Paolo N, Garosi G, Petrini G, Monaci G. Morphological and morphometric changes in mesothelial cells during peritoneal dialysis in the rabbit. Nephron 1996; 74:594-9.
  12. Jörres A, Topley N, Gahl GM. Biocompatibility of peritoneal dialysis fluids. Int J Artif Organs 1992; 15:79-83.
  13. Holmes CJ. Biocompatibility of peritoneal dialysis solutions. Perit Dial Int 1993; 13:88-94.
  14. Gotloib L, Shostak A, Wajsbrot V. Detrimental effects of peritoneal dialysis solutions upon in vivo and in situ exposed mesothelium. Perit Dial Int 1997; 17(Suppl 2):S13-16.
  15. Garosi G, Gaggiotti E, Monaci G, Brardi S, Di Paolo N. Biocompatibility of a peritoneal dialysis solution with amino acids: Histological study in the rabbit. Perit Dial Int 1998; 18:610-19.
  16. Oreopoulos DG, Khanna R, Wu G. Sclerosing obstructive peritonitis after CAPD [Letter]. Lancet 1983; 2:409.
  17. Veech RL, Gitomer WL. The medical and metabolic consequences of administration of sodium acetate. Adv Enzyme Regul 1988; 27:313-23.
  18. Henderson I, Wilson L, Wallace M, Dobbie JW. Sclerosing peritonitis. An experimental study. In: Khanna R, Nolph KD, Prowant B, Twardowski J, Oreopoulos DG, eds. Advances in CAPD. Toronto: Peritoneal Dialysis Bulletin, 1985; 4:107-8.
  19. Junor BRJ, Briggs JD, Forwell MA, Dobbie JW, Henderson I. Sclerosing peritonitis: The contribution of chlorhexidine in alcohol. Perit Dial Bull 1985; 5:101-4.
  20. Guo W, Willen R, Andersson R, et al. Morphological response of the peritoneum and spleen to intraperitoneal biomaterials. Int J Artif Organs 1993; 16:276-84.
  21. Stanley MM, Reyes CV, Greenlee HB, Nemchausky B, Reinhardt GF. Peritoneal fibrosis in cirrhotics treated with peritoneovenous shunting for ascites. An autopsy study with clinical correlations. Dig Dis Sci 1996; 41:571-7.
  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; 17:136-43.
  23. Shaldon S, Koch KM, Quellhorst E. Pathogenesis of sclerosing peritonitis in CAPD. ASAIO Trans 1984; 30:193-4.
  24. Bargman JM, Oreopoulos DG. Complications other than peritonitis or those related to the catheter and the fate of uremic organs dysfunction in patients receiving peritoneal dialysis. In: Nolph KD, ed. Peritoneal dialysis. 3rd edition. Dordrecht: Kluwer Academic Publishers, 1989:289-318.
  25. Sabatini S, Fracasso A, Bazzato G, Kurtzman NA. Effect of phthalate acid esters on transport in toad bladder membrane. J Pharmacol Exp Ther 1989; 250:910-14.
  26. Hetzler AE. The peritoneum. Mosby CV Co., 1919: Chapters 1-2.
  27. Dobbie JW: Pathogenesis of peritoneal fibrosing syndromes (sclerosing peritonitis) in peritoneal dialysis. Perit Dial Int 1992; 12:14-27.
  28. Harty RF. Sclerosing peritonitis and propranolol. Arch Intern Med 1978; 138:1424-6.
  29. Stegmayr BG. Beta-blockers may cause ultrafiltration failure in peritoneal dialysis patients. Perit Dial Int 1997; 17:541-5.
  30. Krediet RT. Beta-blockers and ultrafiltration failure. Perit Dial Int 1997; 17:528-31.
  31. Ahlmén J, Burian P, Eriksson C, Schon S. Sclerosing encapsulating peritonitis once again. Perit Dial Int 1991; 11:279-80.
  32. Dehn TC, Lucas MG, Wood RF. Idiopathic sclerosing peritonitis. Postgrad Med J 1985; 61:841-2.
  33. Comings DE, Skubi KB, Van Eyes J, Motulsky AG. Familial multifocal fibrosclerosis. Findings suggesting that retroperitoneal fibrosis, mediastinal fibrosis, sclerosing cholangitis, Riedel's thyroiditis, and pseudotumor of the orbit may be different manifestations of a single disease. Ann Intern Med 1967; 66:884-92.
  34. Krediet RT. Prevention and treatment of peritoneal dialysis membrane failure. Adv Ren Replace Ther 1998; 5:212-17.
  35. Günal AI, Gezen M, Özercan R, Öner H, Çeliker H. The effect of octreotide on peritoneal alterations induced by high concentrations of glucose. Perit Dial Int 1998; 18:532-40.
  36. Fracasso A, Baggio B, Ossi E, et al. Glycosaminoglycans prevent the functional and morphological peritoneal derangement in an experimental model of peritoneal fibrosis. Am J Kidney Dis 1999; 33:105-10.

Corresponding author:

Guido Garosi, Nephrology and Dialysis Department, Le Scotte Hospital, Viale Bracci 16, I-53100 Siena, Italy.