title: Induction of chronic kidney failure in a long-term peritoneal exposure model in the rat: effects on functional and structural peritoneal alterations.
abstract: BACKGROUND
  A long-term peritoneal exposure model has been developed in Wistar rats. Chronic daily exposure to 3.86% glucose based, lactate buffered, conventional dialysis solutions is possible for up to 20 weeks and induces morphological abnormalities similar to those in long-term peritoneal dialysis (PD) patients. The possible effects of kidney failure in this model are unknown. The aim was to analyze the effects of chronic kidney failure on peritoneal function and morphology, alone and in combination with PD exposure, in a well-established, long term, peritoneal exposure model in the rat. ♢
  
  
  METHODS
  40 male Wistar rats were randomly assigned into four experimental groups: no nephrectomy, no peritoneal exposure (sham; n = 8); nephrectomy, no peritoneal exposure (Nx; n = 12); no nephrectomy, with peritoneal exposure (PD; n = 8); and nephrectomy, with peritoneal exposure (NxPD; n = 12). The nephrectomy consisted of a one-step 70% nephrectomy. The peritoneal exposure groups were infused once daily for 16 weeks with a 3.86% glucose-based dialysis solution. Development of chronic kidney disease was monitored during the experiment. Peritoneal function and morphological assessment of the peritoneal membrane were performed at the end of the experiment. ♢
  
  
  RESULTS
  During follow-up the nephrectomized groups developed uremia with remarkable renal tubular dilatation and glomerular sclerosis in the renal morphology. Functionally, uremia (Nx) and PD exposure (PD) alone showed faster small solute transport and a decreased ultrafiltration capacity, which were most pronounced in the combination group (NxPD). The presence of uremia resulted in histological alterations but the most severe fibrous depositions and highest vessel counts were present in the PD exposure groups (PD and NxPD). Significant relationships were found between the number of vessels and functional parameters of the peritoneal vascular surface area. ♢
  
  
  CONCLUSIONS
  It is possible to induce chronic kidney failure in our existing long-term peritoneal infusion model in the rat. The degree of impairment of kidney function after 16 weeks is comparable to chronic kidney disease stage IV. Uremia per se induces both functional and morphological alterations of the peritoneal membrane. An additive effect of these alterations is present with the addition of chronic kidney failure to the model. The latter makes the present long-term model important in better understanding the pathophysiology of the peritoneal membrane in PD.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: François
authors.initials: F
authors.lastname: Vrtovsnik
authors.forename: Annemieke M
authors.initials: AM
authors.lastname: Coester
authors.forename: Deirisa
authors.initials: D
authors.lastname: Lopes-Barreto
authors.forename: Dirk R
authors.initials: DR
authors.lastname: de Waart
authors.forename: Allard C
authors.initials: AC
authors.lastname: Van der Wal
authors.forename: Dirk G
authors.initials: DG
authors.lastname: Struijk
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Krediet
authors.forename: Machteld M
authors.initials: MM
authors.lastname: Zweers
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001707:Biopsy, Needle; D002408:Catheters, Indwelling; D004195:Disease Models, Animal; D015312:Hemodialysis Solutions / Q000378:metabolism / Q000494:pharmacology*; D007150:Immunohistochemistry; D007676:Kidney Failure, Chronic / Q000503:physiopathology / Q000628:therapy*; D007677:Kidney Function Tests; D016014:Linear Models; D008297:Male; D009392:Nephrectomy / Q000379:methods; D010530:Peritoneal Dialysis / Q000009:adverse effects* / Q000379:methods; D010532:Peritoneal Diseases / Q000209:etiology / Q000473:pathology*; D010537:Peritoneum / Q000187:drug effects* / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012307:Risk Factors; D013997:Time Factors
chemical_list: D015312:Hemodialysis Solutions