title: Atorvastatin improves peritoneal sclerosis induced by hypertonic PD solution in rats.
abstract: BACKGROUND
  Peritoneal sclerosis is a complication of peritoneal dialysis and results in ultrafiltration failure. It is related to chronic peritoneal injury due to dialysis solution content and recurrent peritonitis. Statins have anti-inflammatory properties which may be of value in modulating responses to injury. We evaluated the capacity of atorvastatin to modify peritoneal alterations secondary to hypertonic glucose.
  
  
  METHODS
  Thirty-two non-uremic rats were divided into three groups: group I (Sham) rats received no treatment (n=11), group II received hypertonic (3.86%, 10 ml/day) PD solution (n=10) and group III received hypertonic PD solution (10 ml/day) plus 80 mg/L atorvastatin in drinking water (n=11). After four weeks, a one-hour peritoneal equilibration test (PET) was performed with 3.86% PD solution. Dialysate-to-plasma urea ratio (D/P urea), glucose reabsorption (D 1 /D 0 glucose), ultrafiltration volume (UF), dialysate protein, TGF-beta 1 and VEGF levels were determined.
  
  
  RESULTS
  Administration of atorvastatin resulted in preserved UF (4.9+/-0.8 vs 7.5+/-0.6 mL, p <0.01), protein loss (2.2+/-0.2 vs 2.1+/-0.1 g/L, p >0.05), and peritoneal thickness (53+/-3 vs 26+/-4 microm, p <0.01). D 1 /D 0 glucose was significantly reduced in the dextrose group (0.70+/-0.02 vs 0.56+/-0.04, p <0.01). Both higher levels of TGF-ss 1 (206+/-40 vs 474+/-120 pg/mL, p<0.05), and VEGF in dialysate effluent (4+/-0.4 vs 7.9+/-3 pg/mL, p>0.05), was determined in the dextrose group.
  
  
  CONCLUSIONS
  Exposure to hypertonic glucose solution resulted in alterations in peritoneal transport manifested by a rapid dissipation of the glucose gradient and resultant impaired UF response. Administration of atorvastatin led to prevention of these alterations. We suggest that the anti-inflammatory properties of statins are useful in providing protection of the peritoneal membrane from the effects of hypertonic glucose.
authors.affiliation: Department of Nephrology, Ege University, 35100 Izmir, Turkey. dumans@med.ege.edu.tr
authors.forename: S
authors.initials: S
authors.lastname: Duman
authors.forename: S
authors.initials: S
authors.lastname: Sen
authors.forename: E Y
authors.initials: EY
authors.lastname: Sozmen
authors.forename: D G
authors.initials: DG
authors.lastname: Oreopoulos
mesh_terms: D000818:Animals; D000069059:Atorvastatin; D002784:Cholesterol / Q000032:analysis; D005947:Glucose / Q000032:analysis; D005950:Glucose Solution, Hypertonic / Q000009:adverse effects*; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008297:Male; D008853:Microscopy; D010537:Peritoneum / Q000187:drug effects* / Q000473:pathology*; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012598:Sclerosis; D016212:Transforming Growth Factor beta / Q000032:analysis; D053773:Transforming Growth Factor beta1; D014462:Ultrafiltration; D014508:Urea / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: D005950:Glucose Solution, Hypertonic; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D014508:Urea; D002784:Cholesterol; D000069059:Atorvastatin; D005947:Glucose