Does enalapril prevent peritoneal fibrosis induced by hypertonic (3.86%) peritoneal dialysis solution?
OBJECTIVE
Peritoneal fibrosis (PF) is one of the most serious causes of failure in continuous ambulatory peritoneal dialysis (PD). Although the underlying mechanism responsible for the genesis of PF is still unknown, transforming growth factor beta (TGFbeta1) has been shown to be associated with PF. Angiotensin converting enzyme inhibitors have been shown to prevent the stimulating effect of growth factors. The aim of the present study was to investigate the effect of enalapril on peritoneal function and morphology in a rat model of experimental PF.


METHODS
Twenty-one albino Wistar rats were divided into three groups: (1) the control group (C) received 10 mL isotonic saline intraperitoneally (i.p.), (2) the dextrose (Dx) group 10 mL 3.86% dextrose PD solution i.p., and (3) the enalapril-treated group (ENA) 10 cc 3.86% dextrose PD solution i.p. plus 100 mg/L enalapril in drinking water. After 4 weeks, a 1-hour peritoneal equilibration test was performed with 20 mL 2.27% dextrose PD solution. Dialysate-to-plasma urea ratio (D/P urea), glucose reabsorption (D1/D0 glucose), ultrafiltration (UF) volume, and levels of dialysate protein, TGFbeta1, and cancer antigen 125 (CA125) were determined. The parietal peritoneum was evaluated histologically by light microscopy.


RESULTS
Administration of enalapril resulted in preserved UF (-0.2 +/- 0.7 mL vs 1.7 +/- 0.3 mL, p < 0.05), protein loss (2.3 +/- 0.5 g/L vs 1.6 +/- 0.2 g/L, p > 0.05), and peritoneal thickness (77 +/- 7 microns vs 38 +/- 5 microns, p < 0.001). D/P urea increased significantly in the Dx group (p< 0.05). Both higher levels of TGFbeta1 (undetectable vs 298 +/- 43 pg/mL, p < 0.001) and lower levels of CA125 in dialysate effluent (0.94 +/- 0.5 U/L vs 0.11 +/- 0.1 U/L, p > 0.05) were determined in the Dx group.


CONCLUSIONS
These findings show that peritoneal morphology and function tests were dramatically deranged in the Dx group. The same properties were partially preserved in the ENA group. The production of TGFbeta1 was significantly reduced but peritoneal thickness was not completely inhibited. In conclusion, by inhibiting the production of TGFbeta1, enalapril can preserve peritoneal histology, peritoneal function, and remodeling of mesothelial cells.
Duman
S
S
Department of Nephrology, Ege University Medical School, Izmir, Turkey. dumans@med.ege.edu.tr
Günal
A I
AI
Sen
S
S
Asçi
G
G
Ozkahya
M
M
Terzioglu
E
E
Akçiçek
F
F
Atabay
G
G
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D015314:Dialysis Solutions / Q000009:adverse effects*; D004656:Enalapril / Q000494:pharmacology*; D005355:Fibrosis; D005947:Glucose / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology; D006982:Hypertonic Solutions / Q000009:adverse effects; D008297:Male; D010531:Peritoneal Dialysis, Continuous Ambulatory; D010537:Peritoneum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014508:Urea / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D015314:Dialysis Solutions; D006982:Hypertonic Solutions; D011506:Proteins; D016212:Transforming Growth Factor beta; D004656:Enalapril; D014508:Urea; D005947:Glucose