Pathogenesis of Peritoneal Fibrosing Syndromes (Sclerosing Peritonitis) in Peritoneal Dialysis

Abstract

Drawing from diverse sources including epidemiological and clinical data, surgical observations, histopathology, serosal healing responses to fibrin and fibrinolysis, tissue reaction to chronic exposure, and to exo and endotoxins, new information on mesothelial stem cells, autocrine and paracrine influences on their proliferation and collagen synthesis, and the effect of glucose on fibroconnective tissue, we have begun to piece together the pathogenetic jigsaw of fibrosis in continuous ambulatory peritoneal dialysis (CAPD). The reaction of peritoneal mesothelium and stroma to the stress of continual dialysis results in a spectrum of alterations ranging from opacification through a tanned peritoneum syndrome to sclerosing encapsulating peritonitis (SEP). Any agent that causes irritation of the mesothelial layer and induces serositis, or single severe or multiple episodes of peritonitis resulting in mesothelial loss, predisposes the peritoneum to fibroneogenesis. An accurate definition of the histopathological changes of peritoneal thickening is a prerequisite for defining pathogenesis. This paper is the first attempt to create such a framework. It is evident from many areas of study that fibrin deposition and fibrinolysis, hyalinization of the superficial stromal collagen possibly tanned through nonenzymatic glycosylation by dialysate glucose and the proliferative potential of mesothelial stem cells play an important and possibly interdependent role in excessive fibroneogenesis in certain patients on CAPD. Many of the pieces of the jigsaw are obviously still missing, and the picture is most surely incomplete. Nevertheless, the outline of the pathologic and etiologic landscape should now be discernible.

Apoptosis of Mesothelial Cells Caused by Unphysiological Characteristics of Peritoneal Dialysis Fluids

“…In patients undergoing peritoneal dialysis (PD), the peritoneal cavity is regularly exposed to peritoneal dialysis fluids (PDFs) with unphysiological features. Macroscopically, the mesothelial surface turns brownish ("tanned") during dialysis, a process conveyed by oxidation products of the dextrose used in dialysis solutions (1). Besides this phenomenon, cell degeneration, interstitial edema, and deranged cell biology have all been found in long-term PD treatment (2).…”

Encapsulating peritoneal sclerosis (Review Article)

“…The component of the capsule is fibrin, which oozes from capillary blood vessels outgrowing in the deteriorated peritoneum and firmly covers the surface. 11 Symptoms do not develop in the early stage because the capsule is thin, but bowel obstructive symptoms appear with thickening and shortening of the capsule over time that tighten the intestinal tract. Bowel obstructive symptoms progress slowly rather than violently in many cases because the whole small intestine is tightened.…”

“…Fibrin is considered to be a major component of the capsule, the deposition of which may lead to the development of EPS. 11 Even in a case of early stage PD in which peritoneal deterioration is not yet developed to a significant degree, the disease might readily develop to EPS when intense bacterial peritonitis is complicated. Conversely, in a case of long-term PD with deteriorated peritoneum, EPS might occur even by mild bacterial peritonitis.…”

Preserving the Peritoneal Dialysis Membrane in Long‐Term Peritoneal Dialysis Patients

“…A syndrome of a dry, brown peritoneum (tanned) has been increasingly recognized, which is not peritonitis-associated and is related to the glycosylation of peritoneal collagen. Etiologies of sclerosing peritonitis include acetate (3, clorhexidine (29), glucose, low pH, lactate, PD cessation in the face of an exudative peritoneum, repetitive or severe and prolonged peritonitis, and use of more than 50% dialysate with 4.25 g/dL dextrose (30).…”