The Effects of Renin–angiotensin System Inhibition on Regression of Encapsulating Peritoneal Sclerosis

Abstract

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. Conclusion 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.

Aliskiren ameliorates chlorhexidine digluconate‐induced peritoneal fibrosis in rats

“…A renin-angiotensin system inhibitor could be a powerful tool in preventing the progression of PF. Angiotensin receptor blockers or angiotensin converting-enzyme inhibitors have been shown to ameliorate chlorhexidine gluconate-induced PF in rats [27]. Aliskiren inhibits angiotensin I generation from angiotensinogen by direct renin inhibitors and further decreases angiotensin II production [12].…”

Effects of Renin‐Angiotensin‐Aldosterone System Blockade on Chlorhexidine Gluconate‐Induced Sclerosing Encapsulated Peritonitis in Rats

“…The effect of valsartan in preventing the development SEP has been demonstrated in two studies (5,17). One study demonstrated that valsartan therapy significantly decreased parietal peritoneal thickness and the number of dialysate inflammatory cells, whereas there was no noticeable improvement in other histological outcomes such as neovascularization and fibrosis (17). Another study established that the use of high‐dose valsartan in the experimental model of peritoneal fibrosis reduced the production of dialysate TGF‐β1 and repressed the thickening of the visceral peritoneum (5).…”

“…Otherwise, such molecules as prorenin, renin and aldosterone occurring in the intermediate steps of RAAS were found to increase fibrosis independently of angiotensin II (15,16). In the literature, some authors have suggested that ACE inhibitors and angiotensinogen receptor blockers including olmesartan medoxomil and valsartan may prevent the development of peritoneal fibrosis (17,18). However, there were insufficient data to assess the impact of aliskiren on peritoneal fibrosis.…”

“…The effect of valsartan in preventing the development SEP has been demonstrated in two studies (5,17). One study demonstrated that valsartan therapy significantly decreased parietal peritoneal thickness and the number of dialysate inflammatory cells, whereas there was no noticeable improvement in other histological outcomes such as neovascularization and fibrosis (17).…”

“…It has been reported that the combined use of valsartan and aliskiren in preventing renal fibrosis does not provide any extra benefit as compared to the use of these drugs individually (20). Another study determined that treatment involving a combined use of valsartan and enalapril is not superior to that in which these drugs are used individually (17). As reported in the literature, our study found that a combined use of valsartan and aliskiren did not yield extra benefit with regard to the prevention of peritoneal fibrosis as compared to the invidual use of valsartan.…”