Does Enalapril Prevent Peritoneal Fibrosis Induced by Hypertonic (3.86%) Peritoneal Dialysis Solution?

Abstract

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 p (TGFβ1) 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 (IP), ( 2 ) the dextrose (Dx) group 10 mL 3.86% dextrose PD solution IP, and ( 3 ) the enalapril-treated group (ENA) 10 cc 3.86% dextrose PD solution IP 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, TGFβ1, 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 μ vs 38 ± 5 μ, p < 0.001). D/P urea increased significantly in the Dx group ( p < 0.05). Both higher levels of TGFβ1 (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. Conclusion 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 TGFβ1 was significantly reduced but peritoneal thickness was not completely inhibited. In conclusion, by inhibiting the production of TGFβ1, enalapril can preserve peritoneal histology, peritoneal function, and remodeling of mesothelial cells.

Combination Effect of Lisinopril and Diltiazem as Anti Fibrosis in Peritoneum of Rats

“…In the Study of Duman et al, [40] the used of lisinopril in peritoneal fibrosis of rat showed that there was a significant decrease in TGF-β expression (p<0.05), while on histologic examination showed peritoneum fibrosis reduction compared to dextrose group but it was not statistically significant (p>0.05). In another study, Duman et al [4] used another ACEI like enalapril, obtained high TGF-β results in the CAPD group, undetectable in the control group and CAPD+enalapril (p=0.01) fibroblast peritoneum decreased in CAPD+enalapril compared to CAPD (p>0.05).…”

“…Angiotensin II is considered a growth factor that has a role in cell proliferation, apoptosis, and fibrosis. ACEI that are working with the inhibition of angiotensin II will decrease proteinuria, inflammatory cell infiltration, fibrosis, and growth factor [4,32,33].…”

“…This is consistent to the previous research that TGF-β has a role in mediating the changes on the peritoneal membranes as high-glucose dialysate. Injury in peritoneum is mediated by angiotensin II and correlated with stimulation of AT receptor I [4,40].…”

“…Duman et al [4] provided angiotensin converting enzyme inhibitors (ACEI) in albino Wistar rat that had been given 3.86% intraperitoneal dextrose then, examined the levels of TGF-β and peritoneal morphology. The administration of ACEI resulted in a significant reduction of TGF-β levels, but the peritoneum fibrosis was not fully inhibited [4] Fang, et al [5] discovered that the administration of calcium channel blocker (CCB) could suppress the TGF-β production and assumed that diltiazem was a potential drug in preventing peritoneal fibrosis [5].…”

Influence of Renin‐Angiotensin‐Aldosterone System‐Blocking Drugs on Peritoneal Membrane in Peritoneal Dialysis Patients

“…In experimental animal models, therapy with ACEi was proven to slow the morphological peritoneal membrane alterations associated with glucose exposure through the decrement in angiogenesis and fibrosis (3,4,21). Beneficial effects of RAAS-blocking drugs on peritoneal transport characteristics were also reported in patients treated with PD (3,11,14,15). It was demonstrated that RAAS-blocking drugs prevent the increase in small solute transport, which is probably related to a lower number of peritoneal blood vessels and less fibrosis (3).…”