By reducing production of vascular endothelial growth factor octreotide improves the peritoneal vascular alterations induced by hypertonic peritoneal dialysis solution.
OBJECTIVE
Chronic peritoneal dialysis (PD) may eventually result in vascular alterations of varying degree, which lead to progressive reduction in dialytic efficacy. Although the pathogenesis has not been elucidated yet, vascular endothelial growth factor (VEGF) has been proposed to play a central role in the process leading to vascular alterations.


METHODS
Rats were allocated to three groups: no treatment, intraperitoneal introduction of hypertonic PD solution alone, and intraperitoneal introduction of hypertonic PD solution plus octreotide. After 4 weeks, a 1-hour peritoneal equilibration test (PET) was performed. Dialysate-to-plasma urea ratio (D/P urea), glucose reabsorption (D1/D0 glucose), ultrafiltration volume (UF), and levels of dialysate protein and VEGF were determined. Peritoneal membrane histology was evaluated by light microscopy.


RESULTS
Compared with the control group, rats treated with hypertonic PD solution showed dramatically deranged peritoneal function tests (UF: 5.8 +/- 0.9 mL vs 1.3 +/- 0.6 mL; D/P urea: 0.49 +/- 0.1 vs 0.74 +/- 0.04; D1/D0 glucose: 0.55 +/- 0.05 vs 0.34 +/- 0.06) and morphology (thickness: 4.6 +/- 0.4 mu vs 62 +/- 12 mu; neovascularisation: 0.1 +/- 0.3 vessels per field vs 2.2 +/- 0.3 vessels per field). Similarly, a higher level of VEGF was found in the rats treated with hypertonic PD solution. In rats treated with hypertonic solution plus octreotide, peritoneal thickness was not completely reduced (25 +/- 5 mu), but peritoneal functions were protected (UF: 4.0 +/- 0.5 mL; D/P urea: 0.58 +/- 0.02; D1/D0 glucose: 0.51 +/- 0.02). Moreover, VEGF level and neoangiogenesis were significantly less in the octreotide group than in the group treated with hypertonic dextrose alone.


CONCLUSIONS
Our data document that, by increasing the production of VEGF, a high glucose concentration can cause vascular alterations within the peritoneal membrane. Octreotide can protect against the vascular alterations and preserve peritoneal function by inhibiting overexpression of VEGF and regulating the inflammatory response in the peritoneum.
Günal
Ali Ihsan
AI
Departments of Nephrology, Firat University School of Medicine, Elazig, Turkey. igunal@yahoo.com
Celiker
Hüseyin
H
Akpolat
Nusret
N
Ustündag
Bilal
B
Duman
Soner
S
Akcicek
Fehmi
F
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D015314:Dialysis Solutions / Q000009:adverse effects*; D004195:Disease Models, Animal; D016228:Endothelial Growth Factors / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006982:Hypertonic Solutions / Q000009:adverse effects*; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D008222:Lymphokines / Q000096:biosynthesis*; D008297:Male; D015282:Octreotide / Q000494:pharmacology*; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D010532:Peritoneal Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D010537:Peritoneum / Q000098:blood supply* / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D018931:Antineoplastic Agents, Hormonal; D015314:Dialysis Solutions; D016228:Endothelial Growth Factors; D006982:Hypertonic Solutions; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D015282:Octreotide