mTOR inhibitors for management of encapsulating peritoneal sclerosis: a review of literatures

Ghadimi, Maryam; Dashti‐Khavidaki, Simin; Khalili, Hossein

doi:10.1080/0886022x.2016.1209026

Cited by 12 publications

(16 citation statements)

References 24 publications

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“…In experimental studies, the upregulation of TGF-β and vascular endothelial growth factor has been proven as a crucial step of the initiation of the process that results in fibrosis. TGF-β also regulates many different biological activities such as cell growth, apoptosis, cell differentiation, and ECM synthesis (18). Sirolimus, an inhibitor of mTOR, has anti-inflammatory and anti-fibrotic effects (19).…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Oral Sirolimus Therapy against ESWL-induced Kidney Tissue Damage in Rats

Mercimek¹,

Bostanci²,

Özden³

et al. 2019

jus

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Amaç: Bu çalışmada, deneysel rat modelinde oral sirolimus tedavisinin ekstrakorporeal şok dalgası tedavisi (ESWL) sonrası oluşabilecek böbrek dokusu hasarı üzerine kısa ve uzun dönemde koruyucu etkilerini araştırmayı amaçladık. Gereç ve Yöntem: Bu çalışmada 24 erkek Spraque-Dawley rat kullanıldı. Tüm ratların sol böbreğine 15 kV, 60 SW/dk'da toplam 1000 şok dalgası uyguladı. İki ana grup, ESWL (grup 1) ve ESWL sirolimus (grup 2) oluşturuldu. Her grup erken (E) ve geç (L) olmak üzere iki alt gruba ayrıldı. Sol nefrektomi 15. günde E gruplara, 60. günde L gruplara yapıldı. Tübüler hasar, interstisyel değişiklikler ve skar oluşumu, her denekte en az 10 kortikal alanı için yarı kantitatif olarak skorlandı. Her denek için ortalama bir puan hesaplandı. İstatistiksel analiz için bağımsız örneklem t-testi kullanıldı. İstatistiksel anlamlılık p<0,05 olarak kabul edildi. Objective: In the present study, we aimed to investigate the short-and long-term protective effects of oral sirolimus therapy on extracorporeal shock wave lithotripsy (ESWL)-induced kidney tissue damage in an experimental rat model. Materials and Methods: Twenty-four male Spraque-Dawley rats were used in the study. A total of 1000 shock waves (SWs) were applied to the left kidney of all rats at 15 kV, 60 SW/min. Two main groups, ESWL (group 1) and ESWL sirolimus (group 2), were formed. Each group was divided into two subgroups as early (E) and late (L). Left nephrectomy was performed on the 15 th day in E groups and on the 60 th day in L groups. Tubular injury, interstitial changes, as well as scar formation, were scored semi-quantitatively for at least 10 cortical fields in each sample. An average score was calculated for each subject. Independent samples t-test was used for statistical analysis. The statistical significance was accepted as p<0.05. Results: The mean histopathological score was 0.08±0.94 and 0.15±0.65 (p=0.332) in group 1E and 2E and it was 0.27±0.17 in group 1L and 0.05±0.06 in group 2L, respectively (p<0.05). When group 1E and group 1L were compared, the mean score was 0.08±0.94 and 0.27±0.17, respectively (p<0.05). Furthermore, there was also a statistically significant difference in mean histopathological score between group 2E and group 2L. The mean score was 0.15±0.65 vs 0.05±0.06 (p<0.05). Conclusion: Depending on SW power and frequency, ESWL may cause significant histopathological changes in rat kidneys in the chronic period. In this experimental study, it has been thought that sirolimus treatment may have a tissue protective effect against long-term renal tissue damage.

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Section: Discussionmentioning

confidence: 99%

Protective Effects of Oral Sirolimus Therapy against ESWL-induced Kidney Tissue Damage in Rats

Mercimek¹,

Bostanci²,

Özden³

et al. 2019

jus

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“…63 In a recent review of published case series and reports, the use of inhibitors of mechanistic target of rapamycin (mTOR) like everolimus was reported in 20 patients with PD related encapsulating peritoneal sclerosis and suggested some benefit to patients who had developed EPS after renal transplant, possibly due to the fibrotic action of calcineurin inhibitors. 64 In another report, EPS was detected at a mean of 10.5 months after renal transplantation and of the 10 patients with posttransplant EPS, 5 were treated with mTOR inhibitors and four had a positive outcome. 65 Therefore, a change from calcineurin inhibitors (CNI) to mTORinhibitors may be considered in patients who develop EPS after renal transplantation.…”

Section: Medical Therapymentioning

confidence: 95%

“…65 Therefore, a change from calcineurin inhibitors (CNI) to mTORinhibitors may be considered in patients who develop EPS after renal transplantation. 64 However, most reports have used the drug usually in combination with steroids and/or surgery. It is uncertain if use of medical treatment alone can suffice.…”

Section: Medical Therapymentioning

confidence: 99%

“…67 The patients who develop post-transplant EPS may benefit by decreasing or eliminating the CNI. 64 A report also suggests that use of far-infrared therapy, through antiinflammatory action and stimulation of neoangiogenesis and improved endothelial function through eNOS and HO-1, may improve EPS. 68 In spite of growing evidence of the utility of these agents in treatment of PD related EPS, the evidence in other forms of cocoon is virtually non-existent.…”

Section: Medical Therapymentioning

confidence: 99%

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Abdominal cocoon: An enigmatic entity

Mandavdhare¹

2016

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Abdominal cocoon, variously described as encapsulating peritoneal sclerosis (EPS) or sclerosing encapsulating peritonitis or peritonitis chronica fibrosa incapsulata, represents a syndrome of clinical symptoms related to formation of a fibro-collagenous peritoneal membrane that involves the small intestinal loops. It is the outcome of several different etiologic processes. The major factors associated with development of an abdominal cocoon include continuous ambulatory peritoneal dialysis, tuberculosis, post-renal or liver transplant, use of beta-blockers although a proportion are of idiopathic origin. It is believed that the pathogenesis is driven by epithelial-to-mesenchymal transition of the mesothelial cells. The clinical presentation is related to development of altered gut motility resulting in abdominal pain and features of intestinal obstruction. Surgery is usually required in cases of unremitting intestinal obstruction. Although computed tomography may provide a pre-operative diagnosis, many cases are diagnosed at the time of surgery. Role of conservative therapy using drugs like steroids, tamoxifen, and mechanistic target of rapamycin (mTOR) inhibitors, or antitubercular therapy (in patients with tuberculosis) is uncertain. Early management aimed at the underlying etiological factor may ameliorate the symptoms and halt progression to formation of frank cocoon. Occasionally, conditions like peritoneal carcinomatosis or peritoneal encapsulation may mimic EPS.

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“…Everolimus is an inhibitor of the mammalian target of rapamycin (mTOR) pathway. Due to the anti‐fibrotic and anti‐angiogenesis properties, there have been some experimental and clinical studies suggesting its use in the treatment of EPS 11,12 …”

Section: Introductionmentioning

confidence: 99%

Effect of bevacizumab and everolimus combination treatment on peritoneal sclerosis in an experimental rat model

et al. 2020

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The aim of this study was to investigate whether bevacizumab and everolimus combination therapy is superior to bevacizumab treatment alone as a treatment for peritoneal sclerosis. Forty Wistar albino rats were divided into five equal groups. The control group received isotonic saline solution (2 mL/day) intraperitoneal (IP) daily for 3 weeks. The CG group received 2 mL 0.1% chlorhexidine gluconate (CG) and 15% ethanol dissolved in saline IP daily for 3 weeks. Peritoneal tissue samples were taken at the end of 3 weeks. The resting group received CG (weeks 0‐3), plus isotonic saline solution (2 mL/day) IP daily and tap water (2 mL/day) via a feeding tube daily (weeks 3‐6).The bevacizumab group received CG (weeks 1‐3) plus bevacizumab at 2.5 mg/kg/day (2 mL) IP daily and tap water (2 mL/day) via a feeding tube daily (weeks 3‐6). The bevacizumab+everolimus group received CG (weeks 1‐3) plus bevacizumab at 2.5 mg/kg/day (2 mL) IP daily and everolimus at 0.3 mg/kg/day (2 mL) via a feeding tube daily (weeks 3‐6). Peritoneal tissue samples were taken from these three groups at the end of 6 weeks and were examined after staining with hematoxylin‐eosin and Masson's trichrome. Inflammation, vasculopathy, fibrosis, and peritoneal thickness were evaluated under light microscopy. The samples were also stained with anti‐TGF‐β and anti‐MMP‐2. Inflammation and vasculopathy scores were significantly decreased in the VEGF‐i group compared to the CG group. The addition of everolimus to VEGF‐i showed significantly lower inflammation, vasculopathy, fibrosis scores, and an evident decrease in peritoneal thickening (respectively, 2.29 ± 0.76 vs 0.57 ± 0.53, P = .003; 2.71 ± 0.76 vs 1.43 ± 0.53, P = .008; 2.57 ± 0.79 vs 1.57 ± 0.79, P = .04; 247.5 ± 136.1 vs 84.5 ± 48.6, P = .048). MMP‐2 levels were lower in the combination group compared to the resting group (2.63 ± 0.74 vs 1.86 ± 0.38, P = .019). The study results demonstrated that bevacizumab and everolimus combination therapy was more effective than bevacizumab therapy alone.

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mTOR inhibitors for management of encapsulating peritoneal sclerosis: a review of literatures

Cited by 12 publications

References 24 publications

Protective Effects of Oral Sirolimus Therapy against ESWL-induced Kidney Tissue Damage in Rats

Protective Effects of Oral Sirolimus Therapy against ESWL-induced Kidney Tissue Damage in Rats

Abdominal cocoon: An enigmatic entity

Effect of bevacizumab and everolimus combination treatment on peritoneal sclerosis in an experimental rat model

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