Abstract
Purpose
Encapsulated peritoneal sclerosis (EPS) is a rare complication of long-term peritoneal dialysis (PD) and is usually associated with mortality. Inflammation is a leading factor for developing EPS. This study aimed to investigate the effect of abatacept on peritoneal fibrosis and inflammation using the EPS rat model.
Methods
Twenty-four Wistar albino rats were randomly divided into four equal groups. Group I (control group) was administered isotonic saline (IS) via the intraperitoneal (ip) route during weeks 0–3. Chlorhexidine gluconate (CG) ip was administered to group II (CG group) during weeks 0–3. Group III (CG + IS group) received CG for the first 21 days and IS solution for the following 3 weeks. Group IV (abatacept group) received CG during weeks 0–3, and subsequently, 50 mcg/day abatacept during weeks 4–6. Peritoneal thickness, fibrosis, and inflammation were examined using light microscopy. Expressions of matrix metalloproteinase-2 (MMP-2) and transforming growth factor-beta 1 (TGF-β1) were detected by immunohistochemical staining.
Results
Lesser peritoneal thickness and lower inflammation score were observed in the abatacept group than in the CG and CG + IS groups (p < 0.05). Furthermore, the abatacept group had a lower fibrosis score than the CG + IS group (p < 0.05). MMP-2 and TGF-β1 scores were lower in the abatacept group than in the CG + IS group (p < 0.05).
Conclusions
The results revealed that abatacept had a histopathological beneficial effect on peritoneal fibrosis, inflammation, MMP-2, and TGF-β1 scores, which were induced by CG. Abatacept could be a new therapeutic option for treating EPS.
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References
Garosi G (2009) Different aspects of peritoneal damage: fibrosis and sclerosis. Contrib Nephrol 163:45–53
Murray PJ, Wynn TA (2011) Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol 11:723–737
Habib SM, Abrahams AC, Korte MR et al (2015) CD4 positive T Cells and M2 macrophages dominate the peritoneal infiltrate of patients with EPS. PLoS ONE 10:120–174
Ro Y, Hamada C, Inaba M, Io H, Kaneko K, Tomino Y (2007) Inhibitory effects of matrix metalloproteinase inhibitor ONO-4817 on morphological alterations in chlorhexidine gluconate-induced peritoneal sclerosis rats. Nephrol Dial Transplant 22:2838–2848
Hirahara I, Inoue M, Okuda K, Ando Y, Muto S, Kusano E (2007) The potential of matrix metalloproteinase–2 as a marker of peritoneal injury increased solute transport, or progression to encapsulating peritoneal sclerosis during peritoneal dialysis—a multicentre study in Japan. Nephrol Dial Transplant 22:560–567
Xu T, Xie JY, Wang WM, Ren H, Chen N (2012) Impact of rapamycin on peritoneal fibrosis and transport function. Blood Purif 34:48–57
Nakamoto H (2005) Encapsulating peritoneal sclerosis—a clinician’s approach to diagnosis and medical treatment. Perit Dial Int 25:30–38
Wong CF, Beshir S, Khalil A, Pai P, Ahmad R (2005) Successful treatment of encapsulating peritoneal sclerosis with azathioprine and prednisolone. Perit Dial Int 25:285–287
Morath C, Arns W, Schwenger V et al (2007) Sirolimus in renal transplantation. Nephrol Dial Transplant 22:61–65
Yu CC, Fornoni A, Weins A et al (2013) Abatacept in B7-1—positive proteinuric kidney disease. N Engl J Med 369:2416–2423
Ishii Y, Sawada T, Shimizu A et al (2001) An experimental sclerosing encapsulating peritonitis model in mice. Nephrol Dial Transplant 16:1262–1266
Williams JD, Craig KJ, Topley N et al (2002) Morphologic changes in the peritoneal membrane of patients with renal disease. J Am Soc Nephrol 13:470–479
Jiang S, Tang Q, Rong R et al (2012) Mycophenolate mofetil inhibits macrophage infiltration and kidney fibrosis in long-term ischemia-reperfusion injury. Eur J Pharmacol 688:56–61
Goodlad C, Brown EA (2011) Encapsulating peritoneal sclerosis: what have we learned? Semin Nephrol 31:183–198
Kawanishi H, Watanabe H, Moriishi M, Tsuchiya S (2005) Successful surgical management of encapsulating peritoneal sclerosis. Perit Dial Int 25:39–47
Huddam B, Başaran M, Koçak G et al (2015) The use of mycophenolate mofetil in experimental encapsulating peritoneal sclerosis. Int Urol Nephrol 47:1423–1428
Duman S, Bozkurt D, Sipahi S et al (2008) Effects of everolimus as an antiproliferative agent on regression of encapsulating peritoneal sclerosis in a rat model. Adv Perit Dial 24:104–110
Bozkurt D, Sipahi S, Cetin P et al (2009) Does immunosuppressive treatment ameliorate morphology changes in encapsulating peritoneal sclerosis? Perit Dial Int 29:206–210
Mondello S, Mazzon E, Di Paola R et al (2009) Erythropoietin suppresses peritoneal fibrosis in rat experimental model. Eur J Pharmacol 604:138–149
Mondello S, Mazzon E, Di Paola R et al (2009) Talidomid suppresses peritoneal fibrosis in rat experimental model. Shock 32:332–339
Duman S, Sen S, Duman C, Oreopoulos DG (2005) Effect of valsartan versus lisinopril on peritoneal sclerosis in rats. Int J Artif Organs 28:156–163
Kawanishi H (2005) Encapsuling peritoneal sclerosis. Nephrology 10:249–255
Imai H, Nakamoto H, Fucshima R, Yamanouchi Y, Ishida Y, Suzuki H (2002) Glucocorticoid protects against the development of encapsulating peritoneal sclerosis on peritoneal dialysis. Adv Perit Dial 18:124–130
Lafrance JP, Letourneau I, Ouimet D et al (2008) Successful treatment of encapsuling peritoneal sclerosis with immunosuppressive therapy. Am J Kidney Dis 51:7–10
Wong CF (2006) Clinical experience with tamoxifen in encapsuling peritoneal sclerosis. Perit Dial Int 26:183–184
Holsti MA, Chitnis T, Panzo RJ et al (2004) Regulation of postsurgical fibrosis by the programmed death-1 inhibitory pathway. J Immunol 172:5774–5781
Schmidt DW, Flessner MF (2008) Pathogenesis and treatment of encapsuling peritoneal sclerosis: basic and translational research. Perit Dial Int 28:10–15
Knoerzer DB, Karr RW, Schwartz BD, Mengle-Gaw LJ (1995) Collagen-induced arthritis in the BB rat prevention of disease by treatment with CTLA-4-Ig. J Clin Invest 96:987–993
Ceri M, Unverdi S, Dogan M et al (2012) Effect of sirolimus on the regression of peritoneal sclerosis in an experimental rat model. Int Urol Nephrol 44:977–982
Waller JR, Brook NR, Bicknell GR, Murphy GJ, Nicholson ML (2005) Mycophenolate mofetil inhibits intimal hyperplasia and attenuates the expression of genes favoring smooth muscle cell proliferation and migration. Transplant Proc 37:164–166
Hur E, Bozkurt D, Timur O et al (2012) The effects of mycophenolate mofetil on encapsulated peritoneal sclerosis model in rats. Clin Nephrol 1:1–7
Bozkurt D, Sarsik B, Hur E et al (2011) A novel angiogenesis inhibitor, sunitinib malate, in encapsulating peritoneal sclerosis. J Nephrol 24:359–365
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Bircan, L., Karakose, S., Unverdi, H. et al. Abatacept as a therapeutic option in the treatment of encapsulated peritoneal sclerosis: an experimental rat model. Int Urol Nephrol 49, 909–916 (2017). https://doi.org/10.1007/s11255-017-1535-9
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DOI: https://doi.org/10.1007/s11255-017-1535-9