VASCULAR ENDOTHELIAL GROWTH FACTOR EXPRESSION IN RENAL ALLOGRAFT REJECTION AND CYCLOSPORINE TOXICITY

 

BH Ozdemir, AN Haberal, B Demirhan, M Haberal*

Departments of Pathology and General Surgery*, Baskent University, Faculty of medicine, Ankara-Turkey

 

VEGF is an endothelial mitogen with increased expression in inflammation and vasculopathy. The aim of this study was to clarify the relationship between VEGF expression and macrophage infiltration in renal allografts and to assess the role of VEGF on interstitial fibrosis (IF).

The expression of VEGF and the proportion of macrophage in the interstitium were examined immunohistochemically in 92 cases including 4 cases with non-rejected kidneys, 40 cases with acute rejection (AR), 29 cases with chronic allograft nephropathy (CAN), 10 cases with borderline changes (BD) and 9 cases with CsA toxicity. The follow-up biopsies of all cases with AR were evaluated for the progression of IF.

In the non-rejected group, intraglomerular VEGF expression was observed in endothelial, parietal and visceral cells. Tubular VEGF expression was positive only in few tubules of 2 cases. There was a significant positive correlation between the interstitial macrophage infiltration and tubular VEGF expression (p<0.01). In serial sections interstitial VEGF colocalized with the expression of CD-68 positive macrophages. There were significant differences between the cases with AR, CAN and CsA toxicity for the expression of tubular and interstitial VEGF (p<0.001). Tubular VEGF expression was marked in 17/29 cases (58.6%) of CAN, 9/50 cases (18%) of AR and 3/9 cases (33.3%) of CsA toxicity. A significant difference was found between AR grades with regard to tubular and interstitial VEGF expression  (p<0.01). Patients with AR whose initial biopsies showed marked tubular and interstitial VEGF expression developed IF earlier than those whose initial biopsies showed low grade tubular and interstitial VEGF expression (p<0.05). In addition a significant VEGF expression was observed in the mesangial cells of cases with CAN.

The results suggest that macrophage infiltration and hypoxia due to chronic allograft vasculopathy may play an important role in the induction of VEGF that leads to early IF.

 

 

 

 

 

VASCULAR ENDOTHELIAL GROWTH FACTOR EXPRESSION IN RENAL ALLOGRAFT REJECTION AND CYCLOSPORINE TOXICITY

 

BH Ozdemir, AN Haberal, B Demirhan, M Haberal*

Departments of Pathology and General Surgery*, Baskent University, Faculty of Medicine, Ankara-Turkey

 

 

 

 

Correspondence address:

 

B. Handan  Ozdemir MD

Associate Professor

Department of pathology

Baskent University, Faculty of Medicine

Baglar caddesi  194-6

06700 GOP

Ankara, Turkey

Ph:   +90-312-2126591

Fax: +90-312-2127572

e-mail: handan27@hotmail.com