title: Peritoneal dialysis fluid-induced changes of the peritoneal membrane are reversible after peritoneal rest in rats.
abstract: BACKGROUND
  Peritoneal dialysis (PD) is associated with functional and structural alterations of the peritoneal membrane. However, the (ir)reversibility of these pathological changes of the peritoneum is not understood fully.
  
  
  METHODS
  In an experimental PD model, rats (n = 15) received daily 10 ml conventional glucose containing PD fluid, via peritoneal catheters connected to implanted subcutaneous mini vascular access ports. After 5 weeks of treatment, the first group of animals (PDF; n = 10) was sacrificed, while peritoneal catheters of the remaining group of rats (PD-rest; n = 5) were removed 1 week later. The latter group (PD-rest) was sacrificed 12 weeks after removing catheters. At both time points, untreated rats were included as controls. Cellular and morphological parameters were analysed by light and electron microscopy.
  
  
  RESULTS
  Rats exposed to PD fluid for 5 weeks showed a severe angiogenesis in various peritoneal tissues. Peritoneal rest resulted in a significant reduction in blood vessel density in visceral (mesentery, P<0.05), but not in parietal peritoneum. Five weeks' exposure to PD fluid resulted in a profound fibrosis in the parietal peritoneum, whereas the degree of fibrosis was significantly reduced in the PD-rest group (P<0.02). Daily exposure to PD fluid induced a higher number of mast cells in the omentum compared with untreated rats, whereas peritoneal rest normalized the increased mast cell density completely (P<0.03). Likewise, continued PD fluid instillation evoked a strong omental milky spot response, which was returned to the control level after peritoneal rest (P<0.009). Furthermore, the number of mesothelial cells on the liver was significantly increased in rats treated with PD fluid, whereas animals from the PD-rest group had a lower number of mesothelial cells, although this was not statistically significant (P = 0.08). Finally, as evidenced by electron microscopy, daily exposure to PD fluid resulted in severe damage to the mesothelial cell layer covering the peritoneum, whereas this cell layer was completely recovered after peritoneal rest.
  
  
  CONCLUSIONS
  We show that PD fluid-induced cellular and morphological alterations of the peritoneal membrane are generally reversible.
authors.affiliation: Department of Molecular Cell Biology, VU University Medical Center, Amsterdam, The Netherlands. m.zareie@vumc.nl
authors.forename: Mohammad
authors.initials: M
authors.lastname: Zareie
authors.forename: Eelco D
authors.initials: ED
authors.lastname: Keuning
authors.forename: Piet M
authors.initials: PM
authors.lastname: ter Wee
authors.forename: Robert H J
authors.initials: RH
authors.lastname: Beelen
authors.forename: Jacob
authors.initials: J
authors.lastname: van den Born
mesh_terms: D000818:Animals; D001707:Biopsy, Needle; D015314:Dialysis Solutions / Q000009:adverse effects* / Q000494:pharmacology; D004195:Disease Models, Animal; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D005947:Glucose / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D018919:Neovascularization, Physiologic / Q000502:physiology; D009852:Omentum / Q000187:drug effects* / Q000473:pathology*; D010530:Peritoneal Dialysis / Q000009:adverse effects / Q000379:methods*; D010532:Peritoneal Diseases / Q000209:etiology / Q000473:pathology*; D011336:Probability; D051381:Rats; D017208:Rats, Wistar; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric
chemical_list: D015314:Dialysis Solutions; D005947:Glucose