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

2001 ◽  
Vol 21 (2) ◽  
pp. 219-225 ◽  
Author(s):  
Soner Duman ◽  
Ali Ihsan Günal ◽  
Sait Sen ◽  
Gülay Asçi ◽  
Mehmet Özkahya ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Transforming Growth Factor ◽  
Isotonic Saline ◽  
Control Group ◽  
Peritoneal Fibrosis ◽  
Protein Loss ◽  
Cancer Antigen 125 ◽  
Converting Enzyme Inhibitors ◽  
Plasma Urea ◽  
Peritoneal Function

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.

Itraconazole Attenuates Peritoneal Fibrosis Through Its Effect on the Sonic Hedgehog Signaling Pathway in Mice

2018 ◽  
Vol 48 (6) ◽  
pp. 456-464 ◽  
Author(s):  
Jin Sug Kim ◽  
Kyung Sook Cho ◽  
Seon Hwa Park ◽  
Sang Ho Lee ◽  
Ji Hwan Lee ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Sonic Hedgehog ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Isotonic Saline ◽  
Control Group ◽  
Protective Effects ◽  
Peritoneal Fibrosis ◽  
Shh Signaling ◽  
Itraconazole Treatment

Background: Peritoneal fibrosis is a devastating complication of peritoneal dialysis. However, its precise mechanism is unclear, and specific treatments have not yet been established. Recent evidence suggests that the sonic hedgehog (SHH) signaling pathway is involved in tissue fibrogenesis. Drugs that inhibit this pathway are emerging in the field of anti-fibrosis therapy. Itraconazole, an anti-fungal agent, was also recently recognized as an inhibitor of the SHH signaling pathway. In this study, we used a mouse model to investigate whether the SHH signaling pathway is involved in the development of peritoneal fibrosis and the effects of itraconazole on peritoneal fibrosis. Methods: Peritoneal fibrosis was induced by intraperitoneal (IP) injection of 0.1% chlorhexidine gluconate (CG) solution every other day for 4 weeks, with or without itraconazole treatment (20 mg/kg, IP injection on a daily basis). Male C57BL/6 mice were divided into 4 groups: saline group, saline plus itraconazole group, CG group, and CG plus itraconazole group. Isotonic saline was administered intraperitoneally to the control group. The peritoneal tissues were evaluated for histological changes, expression of fibrosis markers, and the main components of the SHH signaling pathway. Results: Peritoneal thickening was evident in the CG group and was significantly decreased by itraconazole administration (80.4 ± 7.7 vs. 28.2 ± 3.8 µm, p < 0.001). The expression of the following SHH signaling pathway components was upregulated in the CG group and suppressed by itraconazole treatment: SHH, patched, smoothened, and glioma-associated oncogene transcription factor 1. The IP injection of CG solution increased the expression of fibrosis markers such as α-smooth muscle actin and transforming growth factor-β1 in the peritoneal tissues. Itraconazole treatment significantly decreased the expression of these markers. Conclusion: Our study provides the first evidence that the SHH signaling pathway may be implicated in peritoneal fibrosis. It also demonstrates that itraconazole treatment has protective effects on peritoneal fibrosis through the regulation of the SHH signaling pathway. These findings suggest that blockage of the SHH signaling pathway is a potential therapeutic strategy for peritoneal fibrosis.

Can N-Acetylcysteine Preserve Peritoneal Function and Morphology in Encapsulating Peritoneal Sclerosis?

2009 ◽  
Vol 29 (2_suppl) ◽  
pp. 202-205 ◽  
Author(s):  
Devrim Bozkurt ◽  
Ender Hur ◽  
Burcu Ulkuden ◽  
Murat Sezak ◽  
Hasim Nar ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Cell Count ◽  
Degradation Products ◽  
Isotonic Saline ◽  
Control Group ◽  
Albino Rats ◽  
Peritoneal Fibrosis ◽  
Beneficial Effects ◽  
Group 2 ◽  
Wistar Albino Rats

Long-term use of the peritoneum as a dialysis membrane results in progressive irreversible dysfunction, described as peritoneal fibrosis. Oxidative stress during peritoneal dialysis has been established in many studies. Generation of reactive oxygen species (ROS) by conventional peritoneal dialysis solutions, regardless of whether produced by high glucose, angiotensin II, or glucose degradation products may be responsible for progressive membrane dysfunction. The well-known antioxidant molecule N-acetylcysteine (NAC) is capable of direct scavenging of ROS. The aim of the present study was to investigate the effect of NAC therapy on both progression and regression of encapsulating peritoneal sclerosis (EPS). We divided 49 nonuremic Wistar albino rats into four groups: Control group—2 mL isotonic saline intraperitoneally (IP) daily for 3 weeks; CG group—2 mL/200 g 0.1% chlorhexidine gluconate (CG) and 15% ethanol dissolved in saline injected IP daily for a total of 3 weeks; Resting group—CG (weeks 1 – 3), plus peritoneal resting (weeks 4 – 6); NAC-R group—CG (weeks 1 – 3), plus 2 g/L NAC (weeks 4 – 6). At the end of the experiment, all rats underwent a 1-hour peritoneal equilibration test with 25 mL 3.86% PD solution. Dialysate-to-plasma ratio (D/P) urea, dialysate white blood cell count (per cubic milliliter), ultrafiltration (UF) volume, and morphology changes of parietal peritoneum were examined. The CG group progressed to encapsulating peritoneal sclerosis, characterized by loss of UF, increased peritoneal thickness, inflammation, and ultimately, development of fibrosis. Resting produced advantages only in dialysate cell count; with regard to vascularity and dialysate cell count, NAC was more effective than was peritoneal rest. Interestingly, we observed no beneficial effects of NAC on fibrosis. That finding may be a result of our experimental severe peritoneal injury model. However, decreased inflammation and vascularity with NAC therapy were promising results in regard to membrane protection.

scholarly journals Sulodexide Prevents Peritoneal Fibrosis by Downregulating the Expression of TGF-β1 and Its Signaling Pathway Molecules

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Zhiqiang Duan ◽  
Jia Yao ◽  
Nan Duan ◽  
Min Wang ◽  
Shiwei Wang
Keyword(s):  
Peritoneal Dialysis ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Vascular Endothelial Cells ◽  
Inflammatory Factors ◽  
Control Group ◽  
Peritoneal Fibrosis ◽  
Blank Control Group ◽  
Peritoneal Tissue ◽  
Tgf Β1

Peritoneal dialysis is one of the main renal replacement treatments. However, long-term peritoneal dialysis keeps the peritoneum in contact with the sugar-containing nonphysiological peritoneal fluid, which leads to recurrent peritonitis, peritoneal fibrosis, and failure of ultrafiltration. Transforming growth factor-β1 (TGF-β1), related cytokines, and inflammatory factors are closely related to peritoneal fibrosis. Sulodexide (SLX) is a new type of glycosaminoglycan preparation, which is involved in the formation of an anionic charge barrier and can maintain the selective permeability of vascular endothelial cells. In this study, the innovative analysis of SLX specifically prevents the process of peritoneal dialysis peritoneal fibrosis by downregulating the expression of TGF-β1 and its signaling pathway molecules. We randomly divided 30 rats into three groups. The blank control group received no treatment. The peritoneal dialysis model group was injected with 4.25% peritoneal dialysate (PDF) 20 ml daily, and the SLX group was injected with 4.25% PDF 20 ml + sulodexide (SLX) 20 mg/kg daily. After 8 weeks of dialysis, the rats were sacrificed, and the peritoneal function test was performed to determine the amount of glucose transport and ultrafiltration. The thickness of peritoneal per unit area was observed under high magnification. The level of inflammation in peritoneal tissue and the expression of TGF-β1/Smad were detected. The results showed that SLX can significantly improve peritoneal tissue thickening and inflammation, can downregulate the expression of TGF-β1, Smad2, Smad3, and Smad7 in peritoneal tissue, and improve the progression of peritoneal fibrosis.

scholarly journals Curcumin ameliorates peritoneal fibrosis via inhibition of transforming growth factor-activated kinase 1 (TAK1) pathway in a rat model of peritoneal dialysis

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Jun-Li Zhao ◽  
Ting Zhang ◽  
Xia Shao ◽  
Jun-Jun Zhu ◽  
Mei-Zi Guo
Keyword(s):  
Peritoneal Dialysis ◽  
Peritoneal Fluid ◽  
Transforming Growth Factor ◽  
Collagen I ◽  
Control Group ◽  
Sham Operation ◽  
Sprague Dawley ◽  
Peritoneal Fibrosis ◽  
Jnk Pathway ◽  
Tgf Β1

Abstract Background Peritoneal fibrosis (PF) remains a serious complication of long-term peritoneal dialysis (PD). The goal of this study was to investigate the anti-fibrotic effects of curcumin on the PF response to PD and its’ mechanism. Methods Male Sprague–Dawley rats were infused with 20 mL of 4.25% glucose-based standard PD fluid for 8 consecutive weeks to establish PF model and then divided into five groups: Control, received sham operation and 0.9% physiological saline; PD, received 4.25% standard PD fluid; Curcumin, PD rats injected intraperitoeally with curcumin for 8 weeks at doses of 10, 20 or 40 mg/kg. Masson’s staining was performed to evaluate the extent of PF. Peritoneal Equilibration Test (PET) was conducted to assess ultrafiltration volume (UFV) and mass transfer of glucose (MTG), quantitative RT-PCR, and immunohistochemistry or western blotting were performed to measure the expression levels of inflammation and fibrosis-associated factors. We also detected the TGF-β1 in peritoneal fluid by ELISA. Results Compared with the control group, the PD rats showed decreased UFV (2.54 ± 0.48 to 9.87 ± 0.78 mL, p < 0.05] and increased MTG (18.99 ± 0.86 to 10.85 ± 0.65 mmol/kg, p < 0.05) as well as obvious fibroproliferative response, with markedly increased peritoneal thickness (178.33 ± 4.42 to 25.26 ± 0.32um, p < 0.05) and higher expression of a-SMA, collagen I and TGF-β1. Treatment with curcumin significantly increased UFV, reduced MTG and peritoneal thickness of PD rats. The elevated TGF-β1 in peritoneal fluid of PD rats was significantly decreased by curcumin. It attenuated the increase in protein and mRNA of TGF-β1, α-SMA and collagen I in peritoneum of PD rats. The mRNA expressions of TAK1, JNK and p38, as well as the protein expressions of p-TAK1, p-JNK and p-p38 in peritoneum of PD rats were reduced by curcumin. Conclusions Present results demonstrate that curcumin showed a protective effect on PD-related PF and suggest an implication of TAK1, p38 and JNK pathway in mediating the benefical effects of curcumin.

By Reducing Production of Vascular Endothelial Growth Factor Octreotide Improves the Peritoneal Vascular Alterations Induced by Hypertonic Peritoneal Dialysis Solution

2002 ◽  
Vol 22 (3) ◽  
pp. 301-306 ◽  
Author(s):  
Ali Ihsan Günal ◽  
Hüseyin Celiker ◽  
Nusret Akpolat ◽  
Bilal Üstündag ◽  
Soner Duman ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Peritoneal Dialysis ◽  
Growth Factor ◽  
Control Group ◽  
Hypertonic Solution ◽  
Vascular Endothelial ◽  
Peritoneal Membrane ◽  
Plasma Urea ◽  
Endothelial Growth Factor ◽  
Peritoneal Function

Objective Chronic peritoneal dialysis (PD) may eventually result in vascular alterations of varying degree, which lead to progressive reduction in dialytic efficacy. Although the pathogenesis has not been elucidated yet, vascular endothelial growth factor (VEGF) has been proposed to play a central role in the process leading to vascular alterations. Design Rats were allocated to three groups: no treatment, intraperitoneal introduction of hypertonic PD solution alone, and intraperitoneal introduction of hypertonic PD solution plus octreotide. After 4 weeks, a 1-hour peritoneal equilibration test (PET) was performed. Dialysate-to-plasma urea ratio (D/P urea), glucose reabsorption (D1/D0 glucose), ultrafiltration volume (UF), and levels of dialysate protein and VEGF were determined. Peritoneal membrane histology was evaluated by light microscopy. Results Compared with the control group, rats treated with hypertonic PD solution showed dramatically deranged peritoneal function tests (UF: 5.8 ± 0.9 mL vs 1.3 ± 0.6 mL; D/P urea: 0.49 ± 0.1 vs 0.74 ± 0.04; D1/D0 glucose: 0.55 ± 0.05 vs 0.34 ± 0.06) and morphology (thickness: 4.6 ± 0.4 μ vs 62 ± 12 μ; neovascularisation: 0.1 ± 0.3 vessels per field vs 2.2 ± 0.3 vessels per field). Similarly, a higher level of VEGF was found in the rats treated with hypertonic PD solution. In rats treated with hypertonic solution plus octreotide, peritoneal thickness was not completely reduced (25 ± 5 μ), but peritoneal functions were protected (UF: 4.0 ± 0.5 mL; D/P urea: 0.58 ± 0.02; D1/D0 glucose: 0.51 ± 0.02). Moreover, VEGF level and neoangiogenesis were significantly less in the octreotide group than in the group treated with hypertonic dextrose alone. Conclusion Our data document that, by increasing the production of VEGF, a high glucose concentration can cause vascular alterations within the peritoneal membrane. Octreotide can protect against the vascular alterations and preserve peritoneal function by inhibiting overexpression of VEGF and regulating the inflammatory response in the peritoneum.

Risk Factors Responsible for Ultrafiltration Failure in Early Stages of Peritoneal Dialysis

2000 ◽  
Vol 20 (6) ◽  
pp. 631-636 ◽  
Author(s):  
Rafael Selgas ◽  
M.-Auxiliadora Bajo ◽  
M.-José Castro ◽  
Gloria Del Peso ◽  
Abelardo Aguilera ◽  
...  
Keyword(s):  
Risk Factors ◽  
Peritoneal Dialysis ◽  
Control Group ◽  
Diabetic Patients ◽  
Rapid Loss ◽  
The Third ◽  
Early Stages ◽  
Ultrafiltration Failure ◽  
Peritoneal Function ◽  
Over Time

Objective To define risk factors for ultrafiltration failure (UFF) during early stages of peritoneal dialysis (PD). Design Retrospective analysis of a group of patients whose peritoneal function was prospectively followed. Setting A tertiary-care public university hospital. Patients Nineteen of 90 long-term PD patients required a peritoneal resting period to recover UF capacity: 8 had this requirement before the third year on PD (early, EUFF group) and 11 had a late requirement (LUFF group). The remaining 71 patients, those with stable peritoneal function over time, constituted the control group. Main Outcome Measures Peritoneal UF capacity under standard conditions (monthly) and small solute peritoneal transport (yearly). Results None of the conditions appearing at the start of PD or during the observation period could be definitely identified as the cause of UFF. There were no differences in characteristics between the EUFF group and the other two groups, except for the higher prevalence of diabetes in the EUFF group. Residual renal function (RRF) declined in all three groups during the first 2 years, with rapid loss during the third year in the EUFF group. This rapid loss in RRF was coincident with UFF. Peritoneal solute and water transport at baseline was similar in the three groups. After 2 years on PD, individuals in the EUFF group showed a significantly lower UF and higher creatinine mass transfer coefficient values than those in the LUFF group. Diabetic patients in the control group showed remarkable stability in UF capacity over time. During the second year on PD, requirement for increases in dialysate glucose concentration was 3.4 ± 0.5% in the LUFF group, but as high as 25.5 ± 24.2% in the EUFF group. The accumulated days of active peritonitis (APID, days with cloudy effluent) were similar for the three groups after 1, 2, and 3 years on PD. Interestingly, diabetic patients in the control group showed an APID index significantly lower than the overall EUFF group. Diabetics in the control group also had significantly lower APID versus nondiabetics in the control group ( p = 0.016). Conclusions Our findings suggest that certain patients develop early UFF type I. Diabetic state and a higher glucose requirement to obtain adequate UF suggest that glucose on both sides of the peritoneal membrane could be responsible. The mechanisms for this higher requirement remain to be elucidated. The identification of a larger cohort of these early UFF patients should lead to a better exploration of the primary pathogenic mechanisms.

Cytokines and Growth Factors Involved in Peritoneal Fibrosis of Peritoneal Dialysis Patients

2005 ◽  
Vol 28 (2) ◽  
pp. 129-134 ◽  
Author(s):  
K.-H. Oh ◽  
P.J. Margetts
Keyword(s):  
Peritoneal Dialysis ◽  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Fibroblast Growth Factors ◽  
Tissue Growth ◽  
Platelet Derived Growth Factor ◽  
Fibroblast Growth ◽  
Dialysis Patients ◽  
Peritoneal Fibrosis

Peritoneal fibrosis is initiated by exposure of peritoneal tissues to numerous harmful agents encountered during peritoneal dialysis. These agents interact with cells within the peritoneum to induce growth factors and cytokines that are important in the initiation, progression and maintenance of fibrosis. Some of the mediators implicated in the pathogenesis of peritoneal fibrosis include transforming growth factor (TGF) ß, connective tissue growth factor (CTGF), fibroblast growth factors (FGF), and platelet derived growth factor (PDGF).

The Effects of Colchicine on the Progression and Regression of Encapsulating Peritoneal Sclerosis

2008 ◽  
Vol 28 (5_suppl) ◽  
pp. 53-57 ◽  
Author(s):  
Devrim Bozkurt ◽  
Selahattin Bicak ◽  
Savas Sipahi ◽  
Huseyin Taskin ◽  
Ender Hur ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Morphological Changes ◽  
Membrane Integrity ◽  
Isotonic Saline ◽  
Control Group ◽  
Beneficial Effects ◽  
Compact Zone ◽  
Anti Inflammatory ◽  
Group 2 ◽  
Wbc Count

Background Encapsulating peritoneal sclerosis (EPS) is an infrequent but extremely serious complication of long-term peritoneal dialysis. Fibrosis of the submesothelial compact zone and neoangiogenesis underlie the pathophysiology of EPS. Colchicine is a well-known anti-inflammatory and antifibrotic agent that has been used for some fibrosing clinical states, such as liver fibrosis. Objective To determine the antifibrotic and anti-inflammatory effects of colchicine in an EPS rat model in both progression (P) and regression (R). Methods 48 nonuremic albino Wistar rats were divided into 5 groups: control group, 2 mL isotonic saline intraperitoneally (IP) daily for 3 weeks; CG group, IP injection of 2 mL/200 g chlorhexidine gluconate (CG) (0.1%) and ethanol (15%) dissolved in saline, daily for 3 weeks; resting group, CG (0 – 3 weeks) + peritoneal resting (4 – 6 weeks); C-R group, CG (0 – 3 weeks) + 1 mg/L colchicine (4 – 6 weeks); C-P group, CG (0 – 3 weeks) + 1 mg/L colchicine in drinking water (0 – 3 weeks). At the end, a 1-hour peritoneal equilibration test was performed with 25 mL 3.86% peritoneal dialysis solution. Dialysate-to-plasma ratio of urea (D/P urea), dialysate WBC count, ultrafiltration volume, and morphological changes of parietal peritoneum were examined. Result Exposure to CG for 3 weeks resulted in alterations in peritoneal transport (increased D/P urea, decreased ultrafiltration volume; p < 0.05) and morphology (increased inflammation, neovascularization, fibrosis, and peritoneal thickness; p < 0.05). Resting had some beneficial effects on peritoneal derangements; however, once the peritoneum had been stimulated, resting alone was not enough to reverse these pathological changes. Colchicine had more pronounced effects on membrane integrity via decreased inflammation, cell infiltration, and vascularity compared to the resting group. Conclusion We suggest that colchicine may have therapeutic value in the management of EPS.

Lipoprotein (a) Levels in Patients Undergoing Continuous Ambulatory Peritoneal Dialysis

1996 ◽  
Vol 16 (1_suppl) ◽  
pp. 236-241 ◽  
Author(s):  
Carmen Guindeo ◽  
Nicanor Vega ◽  
Ana M. Fernandez ◽  
Leocadia Palop ◽  
Jose A. Aguilar ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Treatment Group ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
The Other ◽  
Control Group ◽  
Protein Loss ◽  
Significant Relation ◽  
Dialysis Treatment ◽  
Lipoprotein A ◽  
Group I

Most researchers have found increases of lipoprotein (a) [Lp(a)] in uremic patients, as well as in those undergo ng hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). The mechanisms for this increase remain unclear. We studied 71 patients undergoing CAPD, 48 me n and 23 women. According to the time spent on CAPD, the patients were divided into three groups: group 0: 29 patients at the starting off point of dialysis treatment; group I: 22 patients with an average stay of 15.2 months; group II: 20 patients with an average stay of 69.3 months on CAPD. We have only observed significant increases of Lp(a) levels in those patients initiating the dialysis, but no significant differences are found in the other groups undergoing CAPD for longer periods when compared to the control group. We found no significant relation between Lp(a) levels and peritoneal protein loss, and not with absorption of glucose from the dialysate either. We have found a positive and significant correlation between Lp(a) levels and urinary protein loss (r = 0.41; p < 0.001). It is possible that an element associated with proteinuria might have an effect on the metabolism of Lp(a) in CAPD patients.

Mineralocorticoid receptor blockade ameliorates peritoneal fibrosis in new rat peritonitis model

2008 ◽  
Vol 294 (5) ◽  
pp. F1084-F1093 ◽  
Author(s):  
Hayato Nishimura ◽  
Yasuhiko Ito ◽  
Masashi Mizuno ◽  
Akio Tanaka ◽  
Yoshiki Morita ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Mineralocorticoid Receptor ◽  
Transforming Growth Factor ◽  
Enzyme Inhibitor ◽  
Smooth Muscle Actin ◽  
Late Phase ◽  
Type Iii Collagen ◽  
Receptor Blockade ◽  
Peritoneal Fibrosis ◽  
Pai 1

Peritoneal fibrosis (PF) is an important complication of long-term peritoneal dialysis. Although mineralocorticoid and mineralocorticoid receptor (MR) have attracted increasing attention in the field of vascular injury, including the heart, kidney, and vessels, little is known about the role of mineralocorticoid in PF. This work was designed to explore the effects of MR blockade on PF. We developed a new model of PF in rats based on mechanical scraping of the peritoneum. This model is characterized by acute-phase inflammation (neutrophil and macrophage infiltration on days 0–3) and late-phase PF (α-smooth muscle actin-positive fibroblast infiltration, type III collagen accumulation, and neoangiogenesis on days 7–14). Peritoneal thickening peaked on day 14. MR was expressed in rat peritoneum and a rat fibroblast cell line. Expression of its effector kinase [serum- and glucocorticoid-induced kinase-1 (Sgk1)], transforming growth factor-β (TGF-β), plasminogen activator inhibitor-1 (PAI-1), and CD31-positive vessels increased during the course of PF. Rats were treated with spironolactone, angiotensin receptor blockade (ARB), or angiotensin-converting enzyme inhibitor (ACEI)-ARB-spironolactone starting at 6 h after peritoneal scraping. All parameters, including peritoneal thickening, number of macrophages and CD31-positive vessels, and expression of monocyte chemoattractant protein-1, TGF-β, PAI-1, and Sgk1, were significantly suppressed by spironolactone (10 mg·kg−1·day−1). The effects of spironolactone (10 and 20 mg·kg−1·day−1) were very similar to those of triple blockade. ARB, but not ACEI, significantly reduced peritoneal thickening. Furthermore, peritoneal function assessed by peritoneal equilibration test was significantly improved by spironolactone. Our results suggest that MR is a potential target to prevent inflammation-induced PF in patients on peritoneal dialysis.

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