The effects of renin-angiotensin system inhibition on regression of encapsulating peritoneal sclerosis.
BACKGROUND
Encapsulating peritoneal sclerosis (EPS) is a clinical syndrome associated with symptoms of ileus and irreversible sclerosis of both visceral and parietal peritoneum. Peritoneal dialysis (PD) patients rarely develop EPS, a severe life-threatening condition of unknown pathogenesis. Angiotensin II is known to promote fibrosis and inflammation in various tissues. Renin-angiotensin system (RAS) blockade provides advantages in the course of diseases such as hypertension, chronic kidney disease, and proteinuria. We have also previously shown that RAS blockade has beneficial effects on hypertonic (3.86%) PD solution-induced peritoneal alterations. Because it shares the same characteristics as other fibrotic processes, peritoneal fibrosis can benefit from RAS blockade.


OBJECTIVE
To determine the advantages of RAS blockade in regression of EPS.


METHODS
We divided 56 nonuremic albino Wistar rats into 6 groups: control group (n = 10), daily intraperitoneal (IP) injection of 2 mL isotonic saline for 3 weeks; CG group (n = 10), daily IP injection of 2 mL/200 g chlorhexidine gluconate (CG) for 3 weeks; resting group (n = 10), daily IP injection of CG (0 - 3 weeks) plus peritoneal rest (4 - 6 weeks). After 3 weeks of being injected with CG (0 - 3 weeks), a fourth group (n = 9) was treated with 100 mg/L enalapril (ENA group); a fifth group (n = 10) was treated with 80 mg/L valsartan (VAL group), and a sixth group (n = 7) was treated with 100 mg/L enalapril + 80 mg/L valsartan (ENA+VAL group) in drinking water for an additional 3 weeks (4 - 6 weeks). At the end, a 1-hour peritoneal equilibration test was performed with 25 mL 3.86% PD solution. Dialysate-to-plasma ratio of urea (D/P urea), dialysate WBC count, ultrafiltration volume (UF), and morphological changes of parietal peritoneum were examined.


RESULTS
Exposure to CG for 3 weeks resulted in alterations in peritoneal transport (increased D/P urea, decreased UF volume; p < 0.05) and morphology (increased inflammation, neovascularization, fibrosis, and peritoneal thickness; p < 0.05). Peritoneal rest had some beneficial effect only on UF failure and dialysate cell count (p < 0.05). However, RAS blockade was more effective than peritoneal rest with respect to UF volume, vascularity (p < 0.05), and peritoneal thickness (p > 0.05). Dual blockade of RAS had no additional beneficial effects.


CONCLUSIONS
We suggest that RAS blockade either with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers may be a more effective option than resting in the management of EPS.
Bozkurt
Devrim
D
Department of Nephrology, Ege University, Izmir, Turkey.
Cetin
Pinar
P
Sipahi
Savas
S
Hur
Ender
E
Nar
Hasim
H
Ertilav
Muhittin
M
Sezak
Murat
M
Duman
Soner
S
D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002710:Chlorhexidine / Q000031:analogs & derivatives; D004195:Disease Models, Animal; D004656:Enalapril / Q000627:therapeutic use*; D005260:Female; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D010537:Peritoneum / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D012598:Sclerosis / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D013777:Tetrazoles / Q000627:therapeutic use*; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068756:Valsartan
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D013777:Tetrazoles; D004656:Enalapril; D000068756:Valsartan; D014633:Valine; C010882:chlorhexidine gluconate; D002710:Chlorhexidine