A novel angiogenesis inhibitor, sunitinib malate, in encapsulating peritoneal sclerosis

作者:Bozkurt Devrim*; Sarsik Banu; Hur Ender; Ertilav Muhittin; Karaca Burcak; Timur Ozge; Bicak Selahattin; Akcicek Fehmi; Duman Soner
来源:Journal of Nephrology, 2011, 24(3): 359-365.
DOI:10.5301/JN.2010.6257

摘要

Introduction: Encapsulated peritoneal sclerosis (EPS) is characterized by neoangiogenesis and fibrosis. Increased inflammation is the leading cause of EPS. In turn, neoangiogenesis is both a consequence of and contributor to inflammation. The effects of sunitinib, a multitargeted receptor tyrosine kinase inhibitor, have been postulated in various antiangiogenesis, antiinflammatory and antifibrotic processes both in vitro and in vivo. This novel angiogenesis inhibitor, Sutent (sunitinib malate), was investigated in our rat EPS model.
Materials and methods: Forty nonuremic Wistar albino rats were divided into 4 groups as follows: 2-mL isotonic saline intraperitoneally (i.p.) daily, for 3 weeks (control group); daily 2 ml/200 g injection i.p. of chlorhexidine gluconate (0.1%) and ethanol (15%) dissolved in saline, 3 weeks (CG group); CG + additional 3 weeks without any treatment, total 6 weeks (resting group); and CG + additional 3 weeks 1 mg/kg daily Sutent (SUT) in drinking water, total 6 weeks (SUT group). At the end of the study, 1-hour PET was performed. Functional parameters and morphological changes of peritoneum with dialysate cytokine levels were examined.
Results: SUT renewed ultrafiltration failure, D-1/D-0 glucose levels and dialysate protein loss. Peritoneal thickness, white blood cell count and inflammation of peritoneum were also decreased with SUT treatment. SUT significantly improved overexpression of dialysate transforming growth factor-beta 1, monocyte chemoattractant protein-1 and vascular endothelial growth factor (VEGF) levels as compared with resting group.
Conclusion: In conclusion, SUT might preserve membrane viability even at lower dosages. Although this is an experimental study, we believe that SUT after controlled trials may be a therapeutic agent for long-term peritoneal dialysis patients.

  • 出版日期2011-6