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Jia R.-P.,Renal Transplantation Center | Ji S.-M.,Chinese PLA General Hospital | Chen J.-S.,Chinese PLA General Hospital | Sun Q.-Q.,Chinese PLA General Hospital | And 5 more authors.
Journal of Clinical Rehabilitative Tissue Engineering Research | Year: 2010

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.

Kishikawa H.,Renal Transplantation Center | Nishimura K.,Renal Transplantation Center | Soda T.,Renal Transplantation Center | Yamanaka K.,Renal Transplantation Center | And 5 more authors.
Transplantation Proceedings | Year: 2010

Objectives We investigated the efficacy and safety of an immunosuppressive regimen consisting of tacrolimus or cyclosporine, with basiliximab, mycophenolate mofetil or mizoribine, and low-dose steroids (prednisone <2.5 mg/d) for kidney transplant recipients. Methods We conducted a prospective study of 51 recipients with stable graft function who underwent kidney transplantation between August 2005 and December 2009. The oral dose of prednisone was gradually tapered to <2.5 mg/d within 2 months after transplantation. We assessed, patient and graft survivals, incidence of rejection episodes, transplant function and steroid side effects. Results Death-censored graft survival was 100%, and the mean serum creatinine levels remained stable at 1.31, 1.37, and 1.48 mg/dL at 1, 2, and 3 years, respectively, after transplantation. There were seven biopsy-proven rejection episodes (mean = 110 days; range = 14436) after prednisone was decreased. The cumulative incidence of biopsy-proven rejection was 11.2%, 17.0%, and 17.0%, respectively. In addition, the mean blood pressure was stable (127/78 mm Hg, 125/77 mm Hg, and 125/76 mmHg, respectively), whereas the mean serum cholesterol and triglyceride levels remained within normal limits. Only 3 patients (7%) displayed new onset diabetes after transplantation. Conclusion Low-dose steroid maintenance therapy is safe with beneficial effects on cardiovascular risk factors. © 2010 Elsevier Inc. All rights reserved.

Guo Q.,Renal Transplantation Center | Huang J.-L.,Renal Transplantation Center | Wang X.-H.,Renal Transplantation Center | Xu D.,Renal Transplantation Center | And 2 more authors.
Journal of Shanghai Jiaotong University (Medical Science) | Year: 2010

Objective: To investigate the effects of different doses of immunodepressant cyclosporine (CsA) on the degree of acute rejection and activity of serum indoleamine 2, 3-dioxygenase (IDO) in rats with allogene heart transplantation. Methods: With SD and Wistar rats as donors and recipients, respectively, rat cervical heterotopic heart transplantation models were established. Eighteen recipients were randomly divided into control group (n = 6) , low-dose CsA group (CsA 2 mg•kg -1•d -1, n =6) and high-dose CsA group (CsA 15 mg•kg -1•d -1, n = 6). Blood samples were taken from abdominal aorta of recipients on the seventh day after transplantation, and heart transplants were harvested for histological examinations. Serum interleukin-2 (IL-2) and interferon-γ (IFN-γ) levels were detected by ELISA, serum kynurenine and tryptophan concentrations were measured by high-pressure liquid chromatography, and the ratios of kynurenine to tryptophan were calculated to estimate the IDO activity. Routine HE staining was performed on samples of heart transplants, and degree of acute rejection was determined with Stanford criteria. Results: For serum IL-2 and IFN-γ levels and IDO activity, there were significant differences among groups ( P < 0. 05 or P < 0. 01) , with control group > low-dose CsA group > high-dose CsA group. For degree of acute rejection of heart transplantation, there were significant differences among groups ( P < 0 . 01), with control group > low-dose CsA group > high-dose CsA group ( P < 0. 01) . Conclusion: CsA may decrease the degree of acute rejection and serum IDO activity in rats with allogene heart transplantation in a dose-dependent manner, and the change of degree of acute rejection is consistent with that of IDO activity. Serum IDO activity may serve as a non-invasive indicator for the prediction and evaluation of acute rejection of transplantation.

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