Abstract:

BACKGROUND: Sirolimus (SRL) has a very important effect on preventing and treating acute rejection in renal transplantation. Moreover, it is a potent inhibitor of smooth muscle cell proliferation and migration, and may play a role in preventing chronic rejection and chronic allograft nephropathy. However, the precise mechanism remains unclear.
OBJECTIVE: To explore the influence of SRL on transforming growth factor-beta 1 (TFG-β1) and vascular endothelial growth factor (VEGF) expression in chronic allograft nephropathy.
METHODS: A total of 60 renal allograft recipients were randomly divided into SRL group, treated by SRL+ cyclosporine A (CsA) +prednisone (Pred), and Azathioprine (Aza) group, treated by Aza +CsA+Pred. SRL was 6 mg and 2 mg per day in 2 weeks, and changed to 1.0-2.0 mg per day after 2 weeks; CsA was 5.0-7.0 mg per day; Aza was 50-100 mg per day, and Pred was 15-20 mg per day. After two years, the pathological changes of the allografts, serum creatinine of the recipients, distribution of TGF-β1 and VEGF, and hepatic function were observed.
RESULTS AND CONCLUSION: The patients were followed-up for 2 years. CsA dose was significantly lower in SRL group than Aza group at 1, 3, 12 months postoperatively, but there were no differences in blood plasma CsA C0 concentration between two groups. In Aza group, TFG-β1 was expressed mostly in proximal convoluted tubule, also in glomerulus and interstitial blood vessel. Majority of tissues expressed TFG-β1 in proximal convoluted tubule, and presented at brush border in line. Some tissues expressed TFG-β1 in glomerular splanchnoderm epithelial cells. Additionally, little TFG-β1 was observed in endothelial cells and intercapillary cells. In SRL group, there was significant decreasing staining in proximal convoluted tubule, but there were no differences in glomerulus and blood vessel. In Aza group, VEGF was expressed mostly in glomerular splanchnoderm epithelial cells, and some in endothelial cells and intercapillary cells. VEGF was positively expressed in interstitial vessel, especially in endothelial layer. There was significant decreasing staining in SRL group glomerulus and blood vessel. Compared with Aza group, patient/kidney survival was high, but VEGF and TFG-β1 expression was significantly decreased. Results from the study showed that SRL decreased VEGF and TFG-β1 expression in renal graft, delayed progression of chronic allograft nephropathy, and prolonged survival of allografts.