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Published on: September 1, 2016
Role of peritubular capillaries and vascular endothelial growth factor in chronic allograft nephropathy
L G Modelli de Andrade1, R M Viero, M F C Carvalho
1Department of Internal Medicine, Botucatu Medical School, São Paulo State University, Botucatu, Brazil. gustavomodelli@yahoo.com.br
Insights
Peritubular capillary damage and vascular endothelial growth factor (VEGF) are key in chronic allograft injury. Reduced peritubular capillaries and increased VEGF correlate with worse graft survival, highlighting their role in kidney transplant outcomes.
Area of Science:
- Nephrology
- Transplantation Immunology
- Pathology
Background:
- Chronic allograft injury is a major cause of kidney transplant failure.
- Peritubular capillaries and vascular endothelial growth factor (VEGF) are implicated in graft dysfunction.
Purpose of the Study:
- To investigate the role of peritubular capillary damage and VEGF in chronic allograft injury.
- To evaluate the correlation of these factors with clinical parameters and graft survival.
Main Methods:
- Histologic analysis of CD34 (peritubular capillaries) and VEGF in 56 kidney transplant recipients with chronic graft dysfunction.
- Classification into chronic allograft injury, cyclosporine toxicity, and control groups.
Main Results:
- CD34 expression decreased with increasing Banff stage and correlated with age and rejection episodes.
- VEGF increased in early chronic allograft injury and nephrotoxicity.
- Low CD34 expression was linked to a higher risk of graft loss (OR 1.45).
Conclusions:
- Peritubular capillaries diminish with chronic allograft injury progression.
- VEGF shows a dynamic pattern, increasing early and decreasing late in nephropathy.
- Loss of peritubular capillaries and VEGF overexpression are associated with poorer kidney allograft survival.
Objective:
To investigate the role of peritubular capillary damage and vascular endothelial growth factor (VEGF) in chronic allograft injury and to evaluate their correlation with clinical factors.
Patients And Methods:
The study included 56 patients who underwent transplantation between 1987 and 2004 and experienced chronic graft dysfunction. CD34 (peritubular capillaries) and VEGF were evaluated at histologic analysis. Patients were classified into 3 groups: 47 with chronic allograft injury, 9 with pure cyclosporine toxicity, and 26 who served as the control group (time 0 biopsy).
Results:
Compared with the control group, CD34 total expression in chronic nephropathy was indirectly proportional to Banff stage (P < .05), and VEGF was increased in chronic allograft injury grade I or II or nephrotoxicity (P < .05). CD34 expression was correlated with age (P < .007) and number of acute rejection episodes (P = .005). A negative correlation was observed between expression of CD34 and of VEGF (P < .001). Low expression of CD34 was associated with risk of graft loss of 1.45 (95% confidence interval, 1.15-7.24; P = .04).
Conclusion:
Peritubular capillaries decreased progressively with development of chronic allograft injury. The VEGF demonstrated a bimodal behavior, increasing at the onset of nephropathy and decreasing in the final stages. Loss of peritubular capillaries was associated with worse graft survival and overexpression of VEGF.
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