Objective To compare the clinical outcomes of pre-emptive renal transplantation and transplantation after dialysis, and to evaluate the safety and advantages of pre-emptive renal transplantation. Methods The data of 50 cases of pre-emptive renal transplantation between January 1999 and January 2003 in our hospital were analyzed.Another 50 cases of renal transplantation after dialysis were selected as control group.The 2 groups were matched in the following variables:age,gender,blood type,cold (warm) ischemic time of the grafts,human leukocyte antigen (HLA),primary diseases, and use of immunosuppressants. The patient/allograft survival,incidence of rejection and delayed graft function were compared. Results The control patients (32/50) were more likely to have received blood transfusion before transplantation than patients of pre-emptive renal transplantation (14/50) (64% vs 28%, P

Objective To explore the clinical outcomes of treatment conversion from cyclosporine A (CsA) based immunosuppression to a new agent tacrolimus (FK506) after kidney tansplantation due to the side effects of CsA. Methods Forty eight cases of kidney transplantation who were diagnosed having CsA hepatoxicity,10 cases having gingival overgrowth,16 cases having hirsuties,and 13 cases having hyperlipidemia were treated with tacrolimus (FK506) in place of CsA.The initial dose of tacrolimus was administered according to the patient's body weight,liver function and time of post operation.The dosage of tacrolimus was adjusted according to its trough level,and the blood levels of tacrolimus were sustained to 8～10 ?g/L within 6 months after operation,6～8 ?g/L within 1 year and 4～6 ?g/L 1 year later.The liver function, renal function,serum lipids level,whole blood FK506 trough concentration,immunosuppressive index and clinical symptoms were closely monitored. Results In 47 of 48 patients who had CsA hepatoxicity and then were treated with FK506 in place of CsA,the liver function became normal 10～48 days later.Only one patient died of liver failure after treatment switch to FK506.All of the 10 patients experienced significant resolution of their gingival enlargement within the time period studied,however only 6 of them had complete regression.All the 16 recipients with hirsuties benefited from replacing CsA with tacrolimus,and were cured after the switch.Lipids levels decreased significantly in the 13 recipients with hyperlipidemia after conversion to tacrolimus. Creatinine levels remained stable and no acute rejection was observed in the study. Conclusions Treatment conversion from CsA to tacrolimus is safe and effective in recipients with hepatic dysfunction,hyperlipidemia or hirsuteness,gingival overgrowth after renal transplantation.The conversion from CsA based immunosuppression to tacrolimus has less side effects and no increase in rejection rate in renal transplant recipients.

Objective To explore the effects of cyclosporin A (CsA) and tacrolimus (Tac) on biological behaviors of lung cancer A549 cells in nude mice.Methods Thirty-six models of transplanted tumor in Balb/c mice were established by using lung cancer A549 cells and divided into three groups:control group,without given any immunosuppressant; CsA group,intraperitoneally given CsA; Tac group,intraperitoneally given Tac.The transplanted tumor growth curve was drawn according to the transplanted tumor volume,and the influencing ratio was calculated according to the final tumor weight.The changes in cell migration ability were observed by using Transwell system.Terminal deoxynucleotidyl transferase mediated UTP nick end labeling (TUNEL) assay was used to examine the apoptosis index of the transplanted tumor.Quantitative RT-PCR was used to detect the expression levels of Bcl-2 mRNA and Bax mRNA.Results The growth of transplanted tumor in CsA and Tac groups was faster than in control group.Final tumor volume and final tumor weight in CsA and Tac groups were greater than those in control group.The influencing ratio in CsA and Tac groups was 19％ (P＜0.05) and 25％ (P＜0.05),respectively.The migration ability was greater in CsA and Tac groups than in control group (P＜0.01).The apoptosis index of the transplanted tumor in CsA and Tac groups was lower than in control group (P＜0.05).The expression level of Bcl-2 mRNA was higher in CsA and Tac groups than in control group (P＜0.05),and that of Bax mRNA was lower in CsA and Tac groups than in control group (P＜0.05).Conclusion Both CsA and Tac can promote the growth of transplanted tumor in nuce mice bearing 549 cells and enhance the invasion forces,which is probably related with the apoptosis induction of tumor cells.

Objective To evaluate the curative effects of conversion from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) on MMF-related chronic diarrhea in the renal transplant (RT) recipients of long-term stage following transplantation.Methods Twenty-six RT recipients with persistent and severe diarrhea,diagnosed as MMF-related diarrhea after a systemic examining procedure including macroscopic and microscopic examinations of the upper and lower gastrointestinal tracks,serology of the blood for CMV and culture of stool for the bacteria.In all the 26 recipients,the dosage of MMF was reduced to 250 mg,twice every day for 2 weeks.Those without significant improvement at the end of this period were shifted to EC-MPS at a dose of 180 mg,twice every day for 2 weeks.The EC-MPS dose was increased to 360 mg,twice every day if the symptoms were improved significantly at the third week after conversion,or EC-MPS was withdrawn if the diarrhea still existed.The dosage of EC-MPS would be reduced to 180 mg,twice every day if the diarrhea recurred in the next 3 months. The clinical symptoms,biological parameters and renal function were observed for 3 months after the conversion.Results ( 1 ) All the 26 recipients were switched to EC-MPS because of the persistent existence of diarrhea after reduction of MMF.After conversion,the diarrhea disappeared completely in 19 out of the 26 recipients in 2 weeks and 2 patients also showed significantly improvement of diarrhea with the total efficiency being 80.8％ (21/26).In the rest 5 cases,EC-MPS was withdrawn at the second week; (2) The disturbance of internal environment was improved significantly following the EC-MPS conversion.Serum potassium,sodium and TCO2 were elevated to normal level.The benefit was predominantly observed in the recipients with moderate to severe proteinuria.The 24-h urinary protein secretion was significantly reduced from 0.76±0.48 to 0.46±0.53 (g/24 h) (P＜0.05) at the third month.Conclusion In RT recipients with MMF-related chronic diarrhea after long-term stage following renal transplantation,switching MMF to EC-MPS can significantly alleviate the diarrhea and rectify the imbalance of internal environment of the recipients.

Objective To assess the change of the CD4~+ CD25~+ Treg after the transplant nephrectomy in recipients suffering from chronic allograft nephropathy (CAN) with normal PRA level.Methods Thirty recipients suffering from CAN,aged 20-55 years old,with norlTlal PRA level,were divided into two groups:removal group (n=17) and preserving group(n=13).CD4~+ CD25~(high)/CD4~+,CTLA-4 and Foxp3 in peripheral blood were tested at two time ends:O month and 2 months after the transplant nephrectomy operation.Results (1) Ratio of CD4~+ CD25~(high)/CD4~+ at the Oth and 2nd month in the removal group was(1.47±0.19)%,(1.08±0.16)%,and that was(1.44±0.25)% and (1.77±0.24)%,at the same time in the preserving group (P<0.01).(2) The expression of CTLA-4 at the Oth and 2nd month in the removal group was (76.82±5.31)% and (72.56±4.99)%,and that was (76.20±4.22)% and (75.24±4.26)% in the preserving group (P>0.05).(3)The expression of Foxp3 was (79.77±1.59)% and (69.07±4.37)% in the removal group,and that was (79.56±1.75)% and (79.09±2.05)% in the preserving group.The expression rate of Foxp3 at the 2nd month in the removal group was significantly lower than in the preserving group (P<0.01).Conclusion Remoral of the graft can reduce the ratio of CD4~+ CD25~(high)/CD4~+ and the expression of Foxp3,suggesting that the removal of the renal graft may inhibit the activity of CD4~+ CD25~+ Treg.

Objective To investigate expression and suppressive function of CD39 + regulatory T cells (Treg) in kidney transplant recipients.Method Thirty recipients of first kidney transplants were treated with tacrolimus,mycophenolate mofetil and prednisone.Within 28 days posttransplantation,there were 14 patients subject to acute rejection (AR group),and the rest 16 patients had no episodes of acute rejections (NR group).Twelve healthy volunteers served as healthy controls (HC group).We collected peripheral blood from the three groups and separated PBMC by density gradient centrifugation,and sorted Tresp,CD39-Treg and CD39+ Treg by flow cytometry.We next analyzed the ratio of CD39 + Treg/CD4+ T cells.ELISA was used to determine the suppressive ability of CD39-Treg and CD39+ Treg on secretion of IFN-γ and IL-17 by Tresp.Results The ratio of CD39 + Treg/CD4 + T cells in AR group was significantly reduced as compared with HC group and NR group (P＜0.05).In HC group and NR group,the secretion of IFN-γ and IL-17 by Tresp was suppressed significantly (P＜0.05) by CD39+ Treg.CD39Treg could suppress secretion of IFN-γ but not IL-17 production by Tresp.CD39+ Treg in AR group AR could suppress the secretion of IFN-γ significantly (P＜0.01),but not to IL-17 production.Conclusion CD39+ Treg have important immunoregulation function.The relative amount of CD39+ Treg was reduced and their regulatory function was impaired in patients with acute rejection.

Objective To summarize the clinical experience of combined liver and kidney transplantation (CLKT). Methods CLKT was performed on 22 patients. The orthotopic liver transplantation (LT) was preceded with the classic fashion in 10 patients and piggyback fashion in 12 patients. The renal allograft was implanted to the iliac fossa routinely. After operation, the patients received an induction therapy with anti-CD25 monoclonal antibody or antithymocyte globulin ( ATG) and a maintenance therapy with tacrolimus (Tac), mycophenolate mofetil and prednisone. Results The CLKT was successfully performed on all 22 patients, and the graft function was restored well postoperation. During the perioperative period, an acute rejection episode of liver occurred in one patient and acute renal allograft rejection episode in 2 patients. The Tac toxicity occurred in one patient. The hemorrhage of digestive tract occurred in one recipient and the hemorrhage of peritoneal cavity in one patient. The pleural effusion occurred in 6 recipients. The pneumonia occurred in 2 cases and the peritoneal infection in one patient During a follow-up period of 6 months to 7 years 11 months, three patients died because of cytomegalovirus pneumonia in 2 patients and acute myocardial infarction in, one patient, The 1-, 3-, 5-year survival rate of recipients was 86,4 %, 81.3 %, 72.7 % respectively. Conclusion The CLKT is an effective method for treatment of patients with end-stage liver djsease and chronic renal failure.

Objective To explore the outcomes of kidney transplant recipients who developed urinary and male genital cancers after transplantation. Methods Data of 31 kidney transplant recipients developed de novo urinary and male genital cancer were compared with data of 31 patients in general population with the same age and same tumor stage. Results Compared with the general population, the overall survival was significantly worse in the transplant recipients (P=0. 02) , 5-year survival rates for each group were 50% vs 68%. Multivariate analyses demonstrated cancer stage to be a negative risk factor for survival for transplant recipients with de novo urinary and male genital cancer, and surgery and functioning graft to be the positive survival predictors. Conclusions Transplant recipients experience worse outcomes than the general population from urinary and male genital cancers. Cancers in transplant recipients are more biologically aggressive at the time of diagnosis.

ObjectiveTo investigate the factors for standard TAC-related nephrotoxicity in renal transplant recipients. MethodsClinical data of 132 patients in TAC-based regiment with a dose of 0. 15-0.3 mg· kg-1 · day-1 and a trough level of 8-11 μg/L during first 2 years post renal transplantation, were retrospectively analyzed. TAC-related nephrotoxicity was diagnosed by renal biopsy and/or clinical criteria. All recipients were divided into 2 groups: TAC nephrotoxicity group (n = 25) and control group (n = 107). Logistic regression analysis was used to rank the relative risk of potential variables including age, gender, delayed graft function (DGF), drug exposure, duration of therapy,liver function, albumin level, hematocrit and gene polymorphism for CYP3A5 and MDR1.ResultsTAC-related nephrotoxicity was found in 25 (18. 9 ％ ) recipients. Univariate and Logistic regression analysis revealed that the influencing factors for TAC-related nephrotoxicity with a standard immunosuppressive regimen and a normal trough level range were identified as: abnormal liver function (RR = 3. 05,95 ％ CI 0. 879-11. 533, P = 0. 024), albumin level (RR = 0. 966,95 ％ CI 0. 994-1. 006, P = 0. 018 ), hematocrit ( RR = 0. 999, 95 ％ CI 0. 998-1. 000, P = 0. 032), CYP3A5 gene polymorphism (RR= 0. 777,95 ％ CI 0. 023-6. 798,P= 0. 032) ,and MDR1 gene polymorphism (RR=0. 654,95 ％ CI 0. 053-7. 109, P = 0. 017). ConclusionLiver function, albumin level, hematocrit, and gene polymorphism for CYP3A5and MDR1as well are influencing factors for TAC-related nephrotoxicity in renal transplant recipients with a standard immunosuppressive regimen and a normal trough level range,in which abnormal liver function is the most important adverse risk factor. These factors should be considered for better individual therapy in renal transplant recipients.

Objective To explore the impact of induction therapy with anti-lymphocyte agents on long-term survival of kidney transplantation.Methods 271 recipients of first cadaveric kidney transplants were treated with tacrolimus,mycophenolate mofetil and prednisone.110 patients of them received induction therapy with anti-thymocyte globulin(ATG group),88 patients received Basiliximab(Bax group),and the remaining 73 patients did not receive induction therapy(control group).The data of AR,DGF,CMV infection,and 1- 3- 5-year patient/allograft survival rate in three groups were retrospectively during a follow-up period of 1 to 5 years postoperatively.Results Within 6 months after operation,the incidence of AR in control group,ATG group and Bax group was 17.8 %(13/73),9.1 %(10/110)and 10.2 %(9/88)respectively.The incidence of AR in ATG group and Bax group was significantly lower than in control group (P<0.05).There was no significant difference in incidence of DGF and CMV infection among three groups.The 1-,3- and 5-year allograft survival rate postoperation in ATG group and Bax group was 95.5 %,90.9 %,87.3 % and 93.2 %,87.5 %,83.8 % respectively,which was significantly higher than in control group(87.7 %,80.8 % and 75.3 %,P<0.05).Conclusion Induction therapy with anti-lymphocyte agents may reduce the early incidence of AR and prolong long-term allograft survival significantly.