Skip to main content
Log in

Abatacept as a therapeutic option in the treatment of encapsulated peritoneal sclerosis: an experimental rat model

  • Nephrology - Original Paper
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Garosi G (2009) Different aspects of peritoneal damage: fibrosis and sclerosis. Contrib Nephrol 163:45–53

    Article  PubMed  Google Scholar 

  2. Murray PJ, Wynn TA (2011) Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol 11:723–737

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. 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

    Google Scholar 

  4. 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

    Article  CAS  PubMed  Google Scholar 

  5. 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

    Article  CAS  PubMed  Google Scholar 

  6. 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

    Article  PubMed  Google Scholar 

  7. Nakamoto H (2005) Encapsulating peritoneal sclerosis—a clinician’s approach to diagnosis and medical treatment. Perit Dial Int 25:30–38

    Google Scholar 

  8. 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

    PubMed  Google Scholar 

  9. Morath C, Arns W, Schwenger V et al (2007) Sirolimus in renal transplantation. Nephrol Dial Transplant 22:61–65

    Google Scholar 

  10. Yu CC, Fornoni A, Weins A et al (2013) Abatacept in B7-1—positive proteinuric kidney disease. N Engl J Med 369:2416–2423

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Ishii Y, Sawada T, Shimizu A et al (2001) An experimental sclerosing encapsulating peritonitis model in mice. Nephrol Dial Transplant 16:1262–1266

    Article  CAS  PubMed  Google Scholar 

  12. 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

    PubMed  Google Scholar 

  13. 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

    Article  CAS  PubMed  Google Scholar 

  14. Goodlad C, Brown EA (2011) Encapsulating peritoneal sclerosis: what have we learned? Semin Nephrol 31:183–198

    Article  PubMed  Google Scholar 

  15. Kawanishi H, Watanabe H, Moriishi M, Tsuchiya S (2005) Successful surgical management of encapsulating peritoneal sclerosis. Perit Dial Int 25:39–47

    Google Scholar 

  16. 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

    Article  CAS  PubMed  Google Scholar 

  17. 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

    CAS  PubMed  Google Scholar 

  18. 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

    Google Scholar 

  19. Mondello S, Mazzon E, Di Paola R et al (2009) Erythropoietin suppresses peritoneal fibrosis in rat experimental model. Eur J Pharmacol 604:138–149

    Article  CAS  PubMed  Google Scholar 

  20. Mondello S, Mazzon E, Di Paola R et al (2009) Talidomid suppresses peritoneal fibrosis in rat experimental model. Shock 32:332–339

    Article  CAS  PubMed  Google Scholar 

  21. 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

    CAS  PubMed  Google Scholar 

  22. Kawanishi H (2005) Encapsuling peritoneal sclerosis. Nephrology 10:249–255

    Article  PubMed  Google Scholar 

  23. 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

    CAS  PubMed  Google Scholar 

  24. 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

    Article  Google Scholar 

  25. Wong CF (2006) Clinical experience with tamoxifen in encapsuling peritoneal sclerosis. Perit Dial Int 26:183–184

    PubMed  Google Scholar 

  26. 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

    Article  CAS  PubMed  Google Scholar 

  27. Schmidt DW, Flessner MF (2008) Pathogenesis and treatment of encapsuling peritoneal sclerosis: basic and translational research. Perit Dial Int 28:10–15

    Google Scholar 

  28. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. 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

    Article  CAS  PubMed  Google Scholar 

  30. 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

    Article  CAS  PubMed  Google Scholar 

  31. 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

    Article  Google Scholar 

  32. Bozkurt D, Sarsik B, Hur E et al (2011) A novel angiogenesis inhibitor, sunitinib malate, in encapsulating peritoneal sclerosis. J Nephrol 24:359–365

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Suleyman Karakose.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-017-1535-9

Keywords

Navigation