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


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, D1/D0 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-ß1, monocyte chemoattractant protein-1 and vascular endothelial growth factor (VEGF) levels as compared with resting group.


CONCLUSIONS
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.
Department of Nephrology, Ege University, Bornova, Izmir - Turkey. devrim_bozkurt@yahoo.com
Devrim
D
Bozkurt
Banu
B
Sarsik
Ender
E
Hur
Muhittin
M
Ertilav
Burcak
B
Karaca
Ozge
O
Timur
Selahattin
S
Bicak
Fehmi
F
Akcicek
Soner
S
Duman
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D056627:Peritoneal Fibrosis / Q000188:drug therapy* / Q000378:metabolism; D011758:Pyrroles / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D000077210:Sunitinib; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D020533:Angiogenesis Inhibitors; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D007211:Indoles; D011758:Pyrroles; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D000077210:Sunitinib