Objective:To study the influence of Costimulatory Blockade CTLA4Ig combined with rapamycin(RPM)on the survival of renal allografts in rats.Methods:BN→Lewis rat kidney transplantation was performed.The recipients were grouped into group1(control),group2(CTLA4Ig),group3(rapamycin,RPM) and group4(CTLA4Ig+RPM).The survival of renal allografts,serum creatinine of the recipients and the pathological changes of the allografts were observed.Results:Significantly prolonged allografts survival time was seen in group 2,3 and 4 compared with control,with the longest in group 4.The lowest serum creatinine and fewest lymphocytes infiltrating grafts were also seen in group4.Conclusion:Combined use of CTLA4Ig and rapamycin(RPM)may suppress renal allograft rejection effectively and promote further prolongation of the survival of renal allografts.

114 ?mol/L continuously) and loss of creatinine clearance (Ccr) were also compared among the 4 groups.For patients with renal dysfunction,the renal biopsies were used to determine whether they had CAN. Results Seventy-seven patients were followed up for 3 years,and their data were analyzed.There were 15 cases in Group A,32 in Group B,18 in Group C,and 12 in Group D.In Groups A,B and C,the expressions of TGF-? 1 protein in the allografts at 7 months after transplantation were (5.82?1.32)?10 6,(6.34? 1.47 )?10 6 and (6.58?1.44)?10 6,and the expressions of TGF-? 1 mRNA were 0.84?0.17,0.78? 0.15 and 0.82?0.16,respectively.In Group D the expressions of TGF-? 1 protein and mRNA were (10.47? 2.12 )?10 6 and 1.37?0.25,which were significantly greater than those in Groups A,B and C ( P

Objective To evaluate the effect of inhibition of transforming growth factor-beta 1 (TGF-?1) expression by liposome-mediated antisense oligonucleotides on chronic nephrotoxicity induced by cyclos-porin A in rats. Methods Rats were on low salt diet and CsA was administered once every day by intraper-itoneal injection (15 mg/kg every day) for 4 weeks. Antisense oligodeoxynucleotides for TGF-?1 were introduced into the nephritic kidney by liposome-mediated gene transfer method to inhibit the overproduction of TGF-?1. Results Under the condition of low salt diet, a rat model of CsA-induced nephrotoxicity was established. The changes of level of serum creatinine and characteristic histopathology of proximal tubular injury and tubulointerstitial fibrosis were observed. In the liposome-mediated AODN rats, the expression of TGF-?1 mRNA was decreased by RT-PCR (P

Objective To study the influence of recipient tolerogenic dendritic cells(DCs) loaded with donor renal antigen on renal allografts survival in rats.Methods Bone marrow derived DCs of Lewis rats were loaded with antigens from donor kidney of BN rats and transferred with AdvCTLA-4Ig to generate tolerogenic DCs.The tolerogenic DCs were injected into the Lewis recipient 24 h before BN→Lewis kidney transplantation(treatment group).Survival time of renal allografts was observed and splenic cell reaction of the recipients to donors and the third party antigens were assayed by means of MTT on the 20~(th)postoperative day.Results Survival time of renal allografts in treatment group was prolonged significantly as compared with controls ((62.1)?(13.7) days vs(8.6)?(0.9) days,P

Objective To investigate the effects of substituting tacrolimus (FK506) for cyclosporine (CsA) on delaying the pace of renal dysfunction in patients with biopsy-proven chronic allograft nephropathy (CAN) and the molecular mechanism of the therapy.Methods From January, 1999 to May, 2002, 93 renal transplant recipients with declining graft function and biopsy-proven CAN (Grade Ⅰ), who had been taking cyclosporine (CsA) as immunosuppressive agent were studied. The patients were randomly divided into group A and group B. CsA was replaced with FK506 (1∶75) in group A that included 50 patients. Group B including the other 43 patients served as control group. All patients were followed up at least three years. Renal functions, losses of creatinine clearance rates within 3 years, incidence of acute renal graft rejection and plasma TGF-?_ 1 concentrations were compared between the two groups.Results Three years later, there were 31 patients ( 62.0 % ) with stabilized or improved graft function in group A, and 4 patients ( 9.3 % ) in group B. The difference was significant (P

Objective To observe the efficacy of CTLA-4Ig gene local transfection on the survival of renal allografts. Methods The kidneys of BN rats were transfected with CTLA-4Ig gene-recombined adenovirus. The transfected kidneys were transplanted to Lewis rats (transfection group). BN→Lewis kidney transplantation with non-transplanted kidneys served as controls. The allograft survival time and the allograft function between the two groups were compared. Results The allograft survival time of transfection group was longer than that of controls significantly (32? 8.0?days vs 8.5 ? 1.4?days , P

Objective To discuss the efficiency and safety of conversion from tacrolimus(Tac)to cyclosporine A(CsA) in patients with new onset diabetes after transplantation (NODAT).Methods The glucose metabolism parameters and related clinical indicators in 45 Tac treated renal transplantation recipients who developed NODAT were retrospectively analyzed.The oral immunosuppressive strategy was Tac + mycophenolate mofetil (MMF) + prednisone(Pred).Results 32 cases were converted to CsA whereas 13 patients stuck to Tac.After conversion,fasting plasma glucose (FPG)decreased from(8.2 ± 2.7)mmol/L to(5.9 ± 1.2)mmol/L(P ＜ 0.01)and HbA1c level decreased from (7.0 ± 0.9) ％ to (6.1 ± 0.7) ％ (P ＜ 0.05).The level of FPG and HbA1c was lower in the conversion group than in the control group(P ＜ 0.05).During the 1-year follow-up,the curative rate of NODAT was 53.1％ (17/32) in the conversion group while it was 0％ in the control group.No acute rejection happened after the conversion.There was no obvious change in renal function.The 1-year survival rate of patient and the transplanted kidney was 100％.Blood pressure and lipid levels were stable after the conversion.Conclusion Conversion from Tac to CsA is a simple and effective strategy to improve glucose metabolism in renal transplantation recipients with NODAT.

Objective To describe the experiences when different methods were used to treat early-onset antibody-mediated rejection (AMR) after kidney transplantation.Methods The clinical data of 42 recipients who experienced early-onset acute AMR after kidney transplantation in our department from Jan.2010 to Apr.2016 were retrospectively analyzed.The recipients were divided into 3 groups based on different strategies against AMR:group A (plasma exchange with intravenous immunoglobin);group B (bortezomib solo),and group C (combination of bortezomib and sirolimus).Results All the AMR episodes were diagnosed by kidney biopsy 9-27 days after transplantation.The AMR reversal rate in groups B and C was significantly higher than that in group A (100％ versus 60.00％,P=0.034;100％ versus 60.00％,P=0.007).The AMR recurrence rate in groups B and C was significantly lower than that in group A (0 versus 41.67％,P =0.035;0 versus 41.67％,P =0.007).The recipient survival rate was 100％ in all the three groups.There were 11 graft losses in group A,and none in group B or C.The graft survival rate in group B at 6 months,1 year and 3 years was significantly higher than in group A (100％ versus 60.00％,P =0.034;100％ versus 55.00％,P =0.021;100％ versus 50.00％,P =0.013).The graft survival rate in group C at 6 months and 1 year was significantly higher than in group A (100％ versus 60.00％,P =0.007;100％ versus 55.00％,P =0.003).There was no significant difference in AMR reversal rate,AMR recurrence rate and graft survival rate between groups B and C.There was no significant difference in incidences of infection,hyperlipidemia and bone marrow suppression among the three groups.The incidence of diarrhea in groups B and C was significantly higher than in group A (50.00％ versus 0,P =0.001;42.86％ versus 0,P =0.001).The incidence of peripheral neuritis in group B was significantly higher than in group A (25.00％ versus 0,P =0.02),but similar to group C.There was no significant difference in average serum creatinine level among three groups within 1 year after treatment (P＞ 0.05).Antibodies against human leukocyte antigen (HLA) and donor specific antibodies were detected in all the 42 recipients before treatment.The negative conversion ratio of panel reactive antibody (PRA) in group A was significantly lower than in groups B and C (10.00％ versus 87.50％,P＜ 0.001;10.00％ versus 92.86％,P ＜ 0.001).The PRA recurrence rate in group A was significantly higher than in groups B and C (85.00％ versus 37.50％,P＜0.001;85.00％ versus 0,P＜0.001),while that in group B was significantly higher than in group C (37.50％ versus 0,P =0.014).The ratio of Treg in peripheral blood at 3-12 month after treatment in group C was significantly higher than in groups A and B (P＜0.05).Conclusion Treatment for early-onset AMR after kidney transplantation based on bortezomib might be an effective and safe strategy.Graft longterm survival might benefit from the combination of bortezomib and sirolimus.

BACKGROUND: Previous studies showed that donor systemic injection of B7/CD28 costimulatory blocker cytotoxic T lymphocyte associated antigen 4 immunoglobulin (CTLA-4Ig) needed in T cell activation can markedly prolong the survival time of rat renal allografts, which, however, has limitations, such as high dose, extensive influence, poor specificity, systemic adverse reactions.OBJECTIVE: In order to improve the targeting of CTLA-4Ig, we modified the dendritic cells of donors and recipients in vitro with CTLA- 4Ig and observed the influence of two kinds of dendritic cells applied alone or together on the survival of renal allografis in rats.DESIGN, TIME AND SETTING: The randomized controlled animal experiment was performed between April 2003 and July 2004 at Laboratory of Department of Urinary Surgery, Xinqiao Hospital, the Third Military Medical University, Chongqing, China.MATERIALS: Kidney donor: inbred Brown-Norway rats, kidney recipient: inbred Lewis rats, unrelated lymphocyte donor: Wistar rats.METHODS: Bone marrow derived dendritic cells of Lewis and Brown Norway rats were modified with CTLA- 4Ig gene recombinant adenovirus in vitro. Animal models of kidney transplantation were built with Brown Norway rats as donors while Lewis rats as recipients. The modified dendritic cells were injected into Lewis rats through femoral vein 24 hours before kidney transplantation alone (group 1 (n=8), donor dendritic cells; group 2 (n=8), recipient dendritic cells) and in combination (group 3 (n=8), donor and recipient dendritic cells). While the recipients without injection were used as control (group 4 (n=6)).MAIN OUTCOME MEASURES: Survival time of renal allografts; the reaction degrees of splenocytes to donor and unrelated antigen determined by MTT method on day 20 postoperation.RESULTS: Survival time of renal allografts in group 2 was not prolonged compared with group 4 while the survival time was markedly prolonged in group 3 (P < 0.01). The response of rat splenocytes to donor antigen in group 1 and group 3 was obviously lower than that in group 4 (P < 0.01), while the response to unrelated antigen was similar to group 4.CONCLUSION: Donor dendritic cells modified with CTLA- 4Ig can significantly prolonged survival time of rat renal allografts and the administration of both donor and recipient dendritic cells modified with CTLA- 4Ig can induce a longer survival time of renal allografts. Recipient dendritic cells cannot prolong the survival time of renal allografts.

Objective To investigate whether reduced or discontinued calcineurin inhibitor (CNI) can improve the renal functions of renal transplant recipients with chronic allograft nephropathy (CAN). Methods A total of 46 renal transplant recipients with declining graft function and biopsy proven CAN were studied. Within 1～2 weeks, CNI (Cyclosporine A or Tacrolimus ) in 27 recipients (group A) was discontinued or reduced to one third of their original doses, but Azathioprine (Aza) or mycophenolate mofetil (MMF) was increased properly. The doses of CNI in the 19 recipients (group B) were not changed obviously, but Aza or MMF was increased properly. At least 1-year follow-up was performed in all patients. Renal functions were compared between the two groups. The incidence of acute renal graft rejection was calculated in both groups. Results One year later, there were 17 patients (63.0%) with stabilized or improved graft function in group A, and 2 (10.5%) in group B. The difference was significant. The incidences of acute rejection in both groups were not significantly different. Conclusion For some renal transplant recipients with declining graft function and biopsy proven CAN, remarkably reduced or discontinued CNI can stabilize or improve their renal functions. Adjusting the doses of immunosuppressive agents does not increase the risk of acute rejection.