抗淋巴细胞制剂诱导治疗对肾移植后人、肾长期存活的影响

目的 探讨抗淋巴细胞制剂诱导治疗对肾移植后人、肾长期存活的影响.方法 271例首次接受尸体肾移植的受者,其中使用抗胸腺细胞球蛋白诱导治疗者110例(ATG组),使用巴利昔单抗诱导治疗者88例(Bax组),未接受诱导治疗者73例(对照组).所有受者术后采用他克莫司+吗替麦考酚酯+皮质激素的三联免疫抑制方案,并应用更昔洛韦预防CMV感染.术后对所有受者进行了1~5年的随访,观察和比较各组术后6个月内的并发症发生情况,以及术后1、3、5年的人、肾存活率.结果 ATG组、Bax组和对照组术后6个月AR的发生率分别为9.1 %(10/110)、10.2 %(9/88)和17.8 %(13/73),ATG组和Bax组间AR发生率的差异无统计学意义(P＞0.05),但均显著低于对照组(P＜0.05).3组间移植肾功能恢复延迟、CMV感染及非CMV感染等发生率的比较,差异均无统计学意义(P＞0.05).ATG组和Bax组术后1、3、5年移植肾存活率分别为95.5 %、90.9 %、87.3 %和93.2 %、87.5 %、83.8 %,均显著高于对照组的87.7 %、80.8 %、75.3 %(P＜0.05).结论 应用抗淋巴细胞制剂进行免疫诱导治疗可显著降低肾移植术后早期AR的发生率,并显著改善移植肾的长期存活率.

Abstract：

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.     

肾移植一年后急性排斥反应时移植肾组织中C4d表达阳性的临床研究

Objective To analyze C4d deposition in the patients with late acute renal allograft rejection,and explore the role of C4d in grafts survival and grafts loss. Methods Thirty-six patients clinical and pathologically diagnosed as having acute rejection more than one year post-transplant were selected. C4d was detected by immunohistochemistry in renal allograft biopsies. The effect of C4d deposition on long-term graft survival was studied. Results Among 36 recipients with late acute renal allograft rejection, 16 cases were positive for C4d (44.4 %) and 20 negative for C4d (55.6 %). Five cases experienced graft loss in C4d positive group (31.3 %), while 6 cases in C4d negative group (30.0%). There was no significant difference in the graft loss rate between C4d-positive group and C4d-negative group. Log-Rank test demonstrated there was no significant difference in graft survival between C4d-positive group and C4d-negative group. The count of the interstitial infiltrated eosinophils in renal allograft was (9.4 + 4.5) and (2.6 + 1.8) respectively in the C4d-positive group and C4dnegative group (P＜0.05). Conclusion C4d deposition in peritubular capillary of the recipients with late acute renal allograft rejection might not be a prognostic marker for graft outcome.     

肾移植一年后急性排斥反应时移植肾组织中C4d表达阳性的临床研究

Objective To analyze C4d deposition in the patients with late acute renal allograft rejection,and explore the role of C4d in grafts survival and grafts loss. Methods Thirty-six patients clinical and pathologically diagnosed as having acute rejection more than one year post-transplant were selected. C4d was detected by immunohistochemistry in renal allograft biopsies. The effect of C4d deposition on long-term graft survival was studied. Results Among 36 recipients with late acute renal allograft rejection, 16 cases were positive for C4d (44.4 %) and 20 negative for C4d (55.6 %). Five cases experienced graft loss in C4d positive group (31.3 %), while 6 cases in C4d negative group (30.0%). There was no significant difference in the graft loss rate between C4d-positive group and C4d-negative group. Log-Rank test demonstrated there was no significant difference in graft survival between C4d-positive group and C4d-negative group. The count of the interstitial infiltrated eosinophils in renal allograft was (9.4 + 4.5) and (2.6 + 1.8) respectively in the C4d-positive group and C4dnegative group (P＜0.05). Conclusion C4d deposition in peritubular capillary of the recipients with late acute renal allograft rejection might not be a prognostic marker for graft outcome.     

小鼠异体Sertoli细胞诱导胰岛移植免疫耐受的作用

Objective To study whether the sertoli cell allograft can achieve the immunotolerance and protect the co-transplant islet allograft on the heterotopic situation. Methods The diabetic C57 mice were used as recipients, and healthy BALB/C mice as islet donors,respectively. Healthy BALB/C and C57 mice were used as testis sertoli cell donors. The recipients were randomly divided into 4 groups,6 mice in each group : group A: only transplant with islet allograft;group B: co-transplant with islet allograft and serto-li isograft;group C:co-transplant with islet allograft and sertoli allograft;group D:sham-operated group. The blood and urine glucose levels in the models, and the survival time of the graft were observed. Results The mean survive time of graft in groups A, B, and C was (6.50±2.35 ), (55.67±4.84), and (51.33± 5.05 ) days respectively. In group D, blood glucose level was abnormal. The hyperglycemia of the diabetic C57 mice could be reversed by the transplant methods of groups B and C. The mean survival time in groups B and C was longer than in group A P < 0.05, but there was no significant differences between groups B and C,P > 0.05. Conclusion The sertoli cells can induce local immunotolerance and protect the co-transplant islet allograft. Sertoli cell isograft can obtain the same local immunotolerance as the sertoli cell allograft.     

小鼠异体Sertoli细胞诱导胰岛移植免疫耐受的作用

Objective To study whether the sertoli cell allograft can achieve the immunotolerance and protect the co-transplant islet allograft on the heterotopic situation. Methods The diabetic C57 mice were used as recipients, and healthy BALB/C mice as islet donors,respectively. Healthy BALB/C and C57 mice were used as testis sertoli cell donors. The recipients were randomly divided into 4 groups,6 mice in each group : group A: only transplant with islet allograft;group B: co-transplant with islet allograft and serto-li isograft;group C:co-transplant with islet allograft and sertoli allograft;group D:sham-operated group. The blood and urine glucose levels in the models, and the survival time of the graft were observed. Results The mean survive time of graft in groups A, B, and C was (6.50±2.35 ), (55.67±4.84), and (51.33± 5.05 ) days respectively. In group D, blood glucose level was abnormal. The hyperglycemia of the diabetic C57 mice could be reversed by the transplant methods of groups B and C. The mean survival time in groups B and C was longer than in group A P < 0.05, but there was no significant differences between groups B and C,P > 0.05. Conclusion The sertoli cells can induce local immunotolerance and protect the co-transplant islet allograft. Sertoli cell isograft can obtain the same local immunotolerance as the sertoli cell allograft.     

小鼠异体Sertoli细胞诱导胰岛移植免疫耐受的作用

Objective To study whether the sertoli cell allograft can achieve the immunotolerance and protect the co-transplant islet allograft on the heterotopic situation. Methods The diabetic C57 mice were used as recipients, and healthy BALB/C mice as islet donors,respectively. Healthy BALB/C and C57 mice were used as testis sertoli cell donors. The recipients were randomly divided into 4 groups,6 mice in each group : group A: only transplant with islet allograft;group B: co-transplant with islet allograft and serto-li isograft;group C:co-transplant with islet allograft and sertoli allograft;group D:sham-operated group. The blood and urine glucose levels in the models, and the survival time of the graft were observed. Results The mean survive time of graft in groups A, B, and C was (6.50±2.35 ), (55.67±4.84), and (51.33± 5.05 ) days respectively. In group D, blood glucose level was abnormal. The hyperglycemia of the diabetic C57 mice could be reversed by the transplant methods of groups B and C. The mean survival time in groups B and C was longer than in group A P < 0.05, but there was no significant differences between groups B and C,P > 0.05. Conclusion The sertoli cells can induce local immunotolerance and protect the co-transplant islet allograft. Sertoli cell isograft can obtain the same local immunotolerance as the sertoli cell allograft.     

小鼠异体Sertoli细胞诱导胰岛移植免疫耐受的作用

Objective To study whether the sertoli cell allograft can achieve the immunotolerance and protect the co-transplant islet allograft on the heterotopic situation. Methods The diabetic C57 mice were used as recipients, and healthy BALB/C mice as islet donors,respectively. Healthy BALB/C and C57 mice were used as testis sertoli cell donors. The recipients were randomly divided into 4 groups,6 mice in each group : group A: only transplant with islet allograft;group B: co-transplant with islet allograft and serto-li isograft;group C:co-transplant with islet allograft and sertoli allograft;group D:sham-operated group. The blood and urine glucose levels in the models, and the survival time of the graft were observed. Results The mean survive time of graft in groups A, B, and C was (6.50±2.35 ), (55.67±4.84), and (51.33± 5.05 ) days respectively. In group D, blood glucose level was abnormal. The hyperglycemia of the diabetic C57 mice could be reversed by the transplant methods of groups B and C. The mean survival time in groups B and C was longer than in group A P < 0.05, but there was no significant differences between groups B and C,P > 0.05. Conclusion The sertoli cells can induce local immunotolerance and protect the co-transplant islet allograft. Sertoli cell isograft can obtain the same local immunotolerance as the sertoli cell allograft.     

小鼠异体Sertoli细胞诱导胰岛移植免疫耐受的作用

Objective To study whether the sertoli cell allograft can achieve the immunotolerance and protect the co-transplant islet allograft on the heterotopic situation. Methods The diabetic C57 mice were used as recipients, and healthy BALB/C mice as islet donors,respectively. Healthy BALB/C and C57 mice were used as testis sertoli cell donors. The recipients were randomly divided into 4 groups,6 mice in each group : group A: only transplant with islet allograft;group B: co-transplant with islet allograft and serto-li isograft;group C:co-transplant with islet allograft and sertoli allograft;group D:sham-operated group. The blood and urine glucose levels in the models, and the survival time of the graft were observed. Results The mean survive time of graft in groups A, B, and C was (6.50±2.35 ), (55.67±4.84), and (51.33± 5.05 ) days respectively. In group D, blood glucose level was abnormal. The hyperglycemia of the diabetic C57 mice could be reversed by the transplant methods of groups B and C. The mean survival time in groups B and C was longer than in group A P < 0.05, but there was no significant differences between groups B and C,P > 0.05. Conclusion The sertoli cells can induce local immunotolerance and protect the co-transplant islet allograft. Sertoli cell isograft can obtain the same local immunotolerance as the sertoli cell allograft.     

小鼠异体Sertoli细胞诱导胰岛移植免疫耐受的作用

Objective To study whether the sertoli cell allograft can achieve the immunotolerance and protect the co-transplant islet allograft on the heterotopic situation. Methods The diabetic C57 mice were used as recipients, and healthy BALB/C mice as islet donors,respectively. Healthy BALB/C and C57 mice were used as testis sertoli cell donors. The recipients were randomly divided into 4 groups,6 mice in each group : group A: only transplant with islet allograft;group B: co-transplant with islet allograft and serto-li isograft;group C:co-transplant with islet allograft and sertoli allograft;group D:sham-operated group. The blood and urine glucose levels in the models, and the survival time of the graft were observed. Results The mean survive time of graft in groups A, B, and C was (6.50±2.35 ), (55.67±4.84), and (51.33± 5.05 ) days respectively. In group D, blood glucose level was abnormal. The hyperglycemia of the diabetic C57 mice could be reversed by the transplant methods of groups B and C. The mean survival time in groups B and C was longer than in group A P < 0.05, but there was no significant differences between groups B and C,P > 0.05. Conclusion The sertoli cells can induce local immunotolerance and protect the co-transplant islet allograft. Sertoli cell isograft can obtain the same local immunotolerance as the sertoli cell allograft.     

小鼠异体Sertoli细胞诱导胰岛移植免疫耐受的作用

Objective To study whether the sertoli cell allograft can achieve the immunotolerance and protect the co-transplant islet allograft on the heterotopic situation. Methods The diabetic C57 mice were used as recipients, and healthy BALB/C mice as islet donors,respectively. Healthy BALB/C and C57 mice were used as testis sertoli cell donors. The recipients were randomly divided into 4 groups,6 mice in each group : group A: only transplant with islet allograft;group B: co-transplant with islet allograft and serto-li isograft;group C:co-transplant with islet allograft and sertoli allograft;group D:sham-operated group. The blood and urine glucose levels in the models, and the survival time of the graft were observed. Results The mean survive time of graft in groups A, B, and C was (6.50±2.35 ), (55.67±4.84), and (51.33± 5.05 ) days respectively. In group D, blood glucose level was abnormal. The hyperglycemia of the diabetic C57 mice could be reversed by the transplant methods of groups B and C. The mean survival time in groups B and C was longer than in group A P < 0.05, but there was no significant differences between groups B and C,P > 0.05. Conclusion The sertoli cells can induce local immunotolerance and protect the co-transplant islet allograft. Sertoli cell isograft can obtain the same local immunotolerance as the sertoli cell allograft.     

Late,Severe, Noninfectious Diarrhea After Renal Transplantation: High-Risk Factors,Therapy, and Prognosis

Objective

Late severe noninfectious diarrhea in renal transplant recipients can lead to malnutrition and even graft loss. The purpose of this study was to evaluate risk factors associated with this condition and summarize therapy for these patients.

Methods

For more than 36 months we observed a cohort of 541 recipients who underwent kidney transplantation from January 2001 to June 2007. They were provided a calcineurin inhibitor (CNI) combined with mycophenolate mofetil (MMF). The four group includes a continuous cyclosporine (CsA); a preconversion to tacrolimus and a postconversion group as well as a continuous tacrolimus group. The rate of severe late noninfectious diarrhea was compared among the four groups. Risk factors were analyzed between the diarrhea and nondiarrhea cohorts. Clinical characteristics, efficacy, and safety were observed after modifying the immunosuppressive protocol for late severe noninfectious diarrhea recipients.

Results

Twenty-eight recipients presented with late sever noninfectious diarrhea. No patients displayed chronic diarrhea in the CsA (n = 145) or preconversion group (n = 95). The rate of diarrhea was 7.31% in the postconversion and 7.35% in the tacrolimus group. Using multivariate Cox proportional hazards analysis, factors associated with an increased risk of noninfectious diarrhea were cytochrome P450(CYP)3A5 *3/*3 type, chronic renal allograft dysfunction, and patient ingestion of Tripterygium wilfordii Hook F. All diarrheal recipients experienced weight loss, hypoalbuminia, and an increased serum creatinine. All affected patients underwent adjustment of the immunosuppressive regimen to achieve remission. Renal allograft survival in recipients with diarrhea was worse than that in nondiarrheal recipients receiving tacrolimus combined with MMF.

Conclusion

Tacrolimus with MMF increased the risk of late severe noninfectious diarrhea among renal transplant recipients compared with hosts treats with CsA plus MMF. The CYP3A5 *3/*3 type, chronic renal allograft dysfunction, and T wilfordii supplementation were high-risk factors for late diarrhea. Prompt adjustment of immunosuppression was an effective, feasible therapy for these patients.     

Impact of Induction Immunosuppression on the Recurrence of Primary IgA Nephropathy

ObjectiveThe objective of this study was to analyze the impact of induction immunosuppression on the incidence of recurrent IgA nephropathy (IgAN).MethodsWe conducted recurrence-free survival analysis of recipients of a first kidney transplant for IgAN who received a graft between 1995 and 2015. Kaplan-Meier and Cox regression analyses were used to sort the significant risk factors for recurrence. A total of 226 recipients with biopsy-proven IgAN received a kidney transplant, and 218 recipients were enrolled.ResultsAmong the recipients, 29 cases of IgAN recurrence were observed. The recipients were categorized into 3 groups according to induction immunosuppression: no induction (group 1, n = 72), anti-CD25 (group 2, n = 86), and antithymocyte globulin (ATG, group 3, n = 60). The 5- and 10-year cumulative IgAN recurrence rates were 9.7% and 21.0%, respectively. Recipients receiving ATG (group 3) exhibited significantly higher 4- and 5-year recurrence-free graft survival rates (both 96.4%) than recipients who received anti-CD25 (group 2, both 85.1%, P = .03). However, the induction therapy used (ATG or basiliximab) was not the risk factor for IgAN recurrence.ConclusionsTherefore, we concluded that ATG induction seems to postpone IgAN recurrence. These findings should be evaluated with well-designed prospective studies.     

Interleukin-2 receptor antagonist does not decrease biopsy-proven acute rejection among adult Chinese kidney transplant recipients

Induction therapy with interleukin-2 receptor antagonist (IL2RA) is widely used for renal transplant recipients and this study aimed to examine the impact of IL2RA among Chinese renal transplant recipients. Two hundred and thirty-eight Chinese renal transplant recipients aged 18-65 years at the Taichung Veterans General Hospital from January 2004 to July 2009 were retrospectively studied to assess the influence of IL2RA on biopsy-proven acute rejection (BPAR) within 1 year. Secondary outcomes included acute rejection rate in the first 3 months, delayed graft function, post-transplant diabetes mellitus, and malignancy. Cox proportional hazard analysis was used for multivariate analysis. Of all the patients, 116 received IL2RA (basiliximab, n = 44; daclizumab, n = 72) and 122 had no induction therapy. The mean follow-up duration was 43.3 months (range, 1-79 months). Overall, 227 (95.4%) patients completed the 12-month follow-up period with a functioning graft. No difference of BPAR was observed between the two groups and the secondary outcomes were also similar. After adjusting potential covariates with Cox regression, IL2RA use still provided no benefit on BPAR. In conclusion, there is no benefit of IL2RA in decreasing BPAR was observed in our study. Routine use of IL2RA for adult Chinese kidney transplant recipients may not be as effective as we thought before. More research is still needed to elucidate the effect of IL2RA among Chinese kidney transplant recipients.     

Effectivity of a T-cell-adapted induction therapy with anti-thymocyte globulin (Sangstat).

BACKGROUND: Cytolytic induction therapy with anti-thymocyte globulin (ATG) should induce effective immunosuppression, with a low rate of rejection in the initial phase after heart transplantation. Induction therapy with ATG allows post-operative renal recovery without the negative effects of highly nephrotoxic cyclosporine levels. An increased rate of infection is a common problem, however, and has been associated with "over-immunosuppression" early after transplantation. Therefore, we investigated whether reduced T-cell-adapted ATG induction therapy could be performed without increasing the risk of graft loss by rejection and whether reductions in infection rates and costs are possible. METHODS: Between March 1999 and December 2002, T-cell-adapted ATG induction therapy with ATG (Sangstat) (1.5 mg/kg) was given to 62 heart transplant recipients (study group) starting on post-operative Days 1 to 6. T-lymphocyte sub-populations were screened daily using flow cytometry. If total lymphocytes were <100/microl (reference 1,300 to 2,300/microl), T-helper lymphocytes (CD4+) <50/microl (reference >500/microl) and T-suppressor cells (CD8+) <50/microl (reference >300/microl), then no ATG was given. Further immunosuppression was continued with triple therapy consisting of methylprednisolone, azathioprine and cyclosporine. An historic group of heart transplant recipients given a full-dose ATG regimen for 8 days served as controls. These recipients were treated with ATG (Merieux 1.5 mg/kg) until reaching monoclonal cyclosporine levels of >300 mg/dl. Additional immunosuppressive treatment did not differ. Patients in both groups received systemic antibiotics (Imipenem) peri-operatively. Results of routine endomyocardial biopsies and rates of infections were examined. RESULTS: Study group patients were older (52 +/- 10 vs 49 +/- 14 years). In the study group, mean cumulative ATG dose was reduced significantly to 596 +/- 220 mg (p < 0.05) for 3.9 +/- 1.6 days compared with 1,159 +/- 376 mg for 6.9 +/- 1.1 days in the control group. The rate of cytomegalovirus (CMV) seroconversion was 23% in the study group compared with 13% in the control group. Rate of deep sternal infections was lower in the study group (1.6% vs 3.2%). The mean rejection rate in the first 3 months was 0.4 +/- 0.7 for the study patients (185 biopsies) vs 1.1 +/- 1.7 for controls (237 biopsies). All biopsies with ISHLT Grade >2 were treated successfully with 1,000 mg of methylprednisolone intravenously for 3 days. Both groups showed a similar 1-year survival rate (study 88%, control 89%). CONCLUSIONS: T-cell-adapted ATG induction therapy can be a helpful tool for individualized immunosuppression. It is not associated with an increased rate of rejection. Lower doses of immunosuppression help to minimize the rates of infection. In addition, cytolytic induction therapy combined with reduced ATG results in significant cost reduction.     

Interleukin-2 Receptor Antagonist Does Not Decrease Biopsy-Proven Acute Rejection among Adult Chinese Kidney Transplant Recipients

Induction therapy with interleukin-2 receptor antagonist (IL2RA) is widely used for renal transplant recipients and this study aimed to examine the impact of IL2RA among Chinese renal transplant recipients. Two hundred and thirty-eight Chinese renal transplant recipients aged 18–65 years at the Taichung Veterans General Hospital from January 2004 to July 2009 were retrospectively studied to assess the influence of IL2RA on biopsy-proven acute rejection (BPAR) within 1 year. Secondary outcomes included acute rejection rate in the first 3 months, delayed graft function, post-transplant diabetes mellitus, and malignancy. Cox proportional hazard analysis was used for multivariate analysis. Of all the patients, 116 received IL2RA (basiliximab, n = 44; daclizumab, n = 72) and 122 had no induction therapy. The mean follow-up duration was 43.3 months (range, 1–79 months). Overall, 227 (95.4%) patients completed the 12-month follow-up period with a functioning graft. No difference of BPAR was observed between the two groups and the secondary outcomes were also similar. After adjusting potential covariates with Cox regression, IL2RA use still provided no benefit on BPAR. In conclusion, there is no benefit of IL2RA in decreasing BPAR was observed in our study. Routine use of IL2RA for adult Chinese kidney transplant recipients may not be as effective as we thought before. More research is still needed to elucidate the effect of IL2RA among Chinese kidney transplant recipients.     

Comparison of single bolus ATG and Basiliximab as induction therapy in presensitized renal allograft recipients receiving tacrolimus-based immunosuppressive regimen

Presensitized renal allograft recipients require special management to improve their outcome, and there is no consensus on the optimal immunosuppressive strategy. We retrospectively analyzed clinical data of 82 patients, who were PRA positive pre-transplant (above 10%) and received single bolus ATG and basiliximab as induction therapy, and assessed safety and efficacy of two kinds of induction therapies. Patients of ATG group (n=40) received single bolus ATG (Fresenius, 9 mg/kg preoperatively) and those of basiliximab group (n=42) were given two doses of basiliximab (Simulect, Novartis, 20 mg) on days 0 and 4 post-transplant. All patients received standard triple immunosuppressive therapy with tacrolimus (FK-506), mycophenolate mofetil (MMF), and steroids. The follow-up time was 12 months. There was no hyperacute rejection in two groups, and delayed graft function occurred in two patients of ATG group and three of basiliximab group. After 12-month follow-up, more acute rejection (AR) episodes were observed in basiliximab group than ATG group (35.7% vs. 15%, P=0.032). Although highly significant differences were observed between ATG group and basiliximab group with respect to the incidence of thrombocytopenia (P=0.001), single bolus ATG was well tolerated. Incidences of other adverse events and infection episodes did not differ between two groups (P>0.05). One-year patient and graft survival was 95%, 92.5% and 95.2%, 88.1% in ATG and basiliximab group respectively (P>0.05). Both single bolus ATG and basiliximab induction therapy achieved similar one-year graft/patient survival. However, single bolus ATG yielded much lower AR rate than basiliximab without increase in infection episodes and severe adverse events.     

Improved clinical outcomes in Chinese renal allograft recipients receiving lower dose immunosuppressants

BACKGROUND: The application of potent immunosuppressants has decreased the incidence of acute rejection and increased short- and long-term graft survival; however, these drugs cause a variety of complications. In China, many transplant centers have adopted the immunosuppressive protocols based on the white population, neglecting the differences between the races. The purpose of this study was to explore a suitable immunosuppressive regimen for Chinese renal allograft recipients. METHODS: Two hundred cadaveric renal allograft recipients who underwent transplantation between July 1999 and October 2001 were observed. Before October 2000, 104 recipients received the conventional dose of immunosuppressants; thereafter, 96 recipients received lower dose treatment. Doses of immunosuppressive agents, the incidence of acute rejection and pulmonary infection, and patient and graft survival rates were compared between the two groups. RESULTS: Doses of mycophenolate mofetil (MMF) and cyclosporine A (CsA) administered in the conventional dose group were significantly higher than in the lower dose group at 3 months posttransplant, as was prednisone at 6 months posttransplant. The incidence of acute rejection and subclinical rejection that was biopsy-proven or diagnosed by clinical manifestations was 17.3% and 19.8%, respectively, in the conventional dose group and the lower dose group within the first 6 months, and no significant difference was noted (P=0.55). The incidence of pulmonary infection, especially severe infection, was much higher in the conventional treatment group (40.1% and 26.9%, respectively) than that in the lower dose group (11.5% and 5.2%, respectively), and the differences were statistically significant (P<0.001). The corresponding 1-year survival rate of patients was 87.4% and 97.9% (P<0.01), and that of renal grafts was 85.5% and 96.9% (P<0.01), for patients receiving conventional dose and lower dose immunosuppressive drugs, respectively. The rate of death with a functioning allograft caused by infection in the conventional dose group was significantly higher than that in the lower dose group (12.5% vs. 0%, P<0.01). CONCLUSIONS: The regimen of lower dose MMF, CsA, and prednisone in combination can significantly reduce the incidence of pulmonary infection, especially severe pulmonary infection, without increasing the incidence and severity of allograft rejection.     

Identifying risk profiles in liver transplant candidates and implications for induction immunosuppression

Changes in recipient and donor characteristics are redefining the role of induction in liver transplant recipients. Older recipients are more common, with greater concomitant comorbidity. Moderate or severe renal dysfunction is now estimated to affect 40% of liver transplant recipients. Donors are also becoming older, and other factors such as more frequent non-alcoholic fatty liver disease (NAFLD) compromise the quality of some grafts. Rejection rates are now relatively low (~10%) but some patients have a markedly increased risk such as younger recipients and those undergoing re-transplantation. Induction immunosuppression is associated with a significant reduction in rejection risk but due to various factors universal induction is not justified. Steroid-free therapy without induction increases the risk of biopsy-proven acute rejection (BPAR) but randomized trials have shown that induction with an interleukin-2 antagonist receptor (IL-2RA) agent or with rabbit antithymocyte globulin (rATG) maintains immunosuppressive efficacy in steroid-free regimens. Delayed calcineurin inhibitor (CNI) initiation (e.g. to days 4?5 post-transplant) can prevent deterioration of renal function during the first year post-transplant, but requires induction with an IL-2RA agent or rATG to maintain early immunosuppressive efficacy. IL-2RA induction may be inadequate to ensure a low risk of rejection in a steroid-free regimen combined with delayed tacrolimus. Randomized trials of CNI withdrawal at month 1 post-transplant have only achieved an acceptable rate of BPAR when induction is administered. In terms of safety, an increased rate of infection does not seem to be a concern. The most recent large-scale analyses have not indicated any evidence for an increased risk of malignancy, or specifically post-transplant lymphoproliferative disease. In summary, the place of induction in the management of liver transplant patients is becoming established. Selective use in high-risk individuals to avoid graft rejection is still relevant, but the key rationale for induction is to facilitate steroid-sparing and CNI-sparing regimens to reduce long-term complications.     

Immunosuppression With CD40 Costimulatory Blockade Plus Rapamycin for Simultaneous Islet–Kidney Transplantation in Nonhuman Primates

The lack of a reliable immunosuppressive regimen that effectively suppresses both renal and islet allograft rejection without islet toxicity hampers a wider clinical application of simultaneous islet–kidney transplantation (SIK). Seven MHC‐mismatched SIKs were performed in diabetic cynomolgus monkeys. Two recipients received rabbit antithymocyte globulin (ATG) induction followed by daily tacrolimus and rapamycin (ATG/Tac/Rapa), and five recipients were treated with anti‐CD40 monoclonal antibody (mAb) and rapamycin (aCD40/Rapa). Anti‐inflammatory therapy, including anti–interleukin‐6 receptor mAb and anti–tumor necrosis factor‐α mAb, was given in both groups. The ATG/Tac/Rapa recipients failed to achieve long‐term islet allograft survival (19 and 26 days) due to poor islet engraftment and cytomegalovirus pneumonia. In contrast, the aCD40/Rapa regimen provided long‐term islet and kidney allograft survival (90, 94, >120, >120, and >120 days), with only one recipient developing evidence of allograft rejection. The aCD40/Rapa regimen was also tested in four kidney‐alone transplant recipients. All four recipients achieved long‐term renal allograft survival (100% at day 120), which was superior to renal allograft survival (62.9% at day 120) with triple immunosuppressive regimen (tacrolimus, mycophenolate mofetil, and steroids). The combination of anti‐CD40 mAb and rapamycin is an effective and nontoxic immunosuppressive regimen that uses only clinically available agents for kidney and islet recipients.     

不同抗体的诱导治疗在再次肾移植中应用效果的比较

目的 总结在再次肾移植中采用抗体进行免疫诱导的临床经验,并比较不同抗体的应用效果.方法 回顾分析39例再次肾移植受者的临床资料.39例受者均接受了免疫诱导,其中接受巴利昔单抗(Bax)者12例(Bax组),接受抗胸腺细胞球蛋白(ATG)者8例(ATG组),接受抗淋巴细胞球蛋白(ALG)者19例(ALG组).观察和比较各组间急性排斥反应(AR)、移植物功能丧失、巨细胞病毒(CMV)感染等发生率,以及术后1年时血清肌酐(SCr)水平和移植肾存活率.结果 Bax 组、ALG组和ATG组分别有41.7 ％(5/12)、47.4％(9/19)和12.5％(1/8)的受者发生AR,ATG组AR发生率明显低于Bax组和ALG组(P＜0.05),而Bax组和ALG组间的差异无统计学意义.39例移植肾1年总体存活率为84.6％,Bax组、ALG组和ATG组分别为82.4％、80.5％和90.8％,ATG组显著高于其他2组(P＜0.05);3组术后1年时SCr值分别为(176.8±43.5) μmol/L、(195.4±35.2) μmol/L、(121.3±22.6) μmol/L,ATG组的SCr水平显著低于其他2组(P＜0.0)5),而Bax组与ALG组间SCr水平的差异无统计学意义.Bax组、ALG组和ATG组CMV感染发生率分别为16.7％(2/12)、15.8 ％(3/19)和25％(2/8),3组间两两比较,差异均无统计学意义(P＞0.05).结论 再次肾移植受者具有较高的免疫风险因素及AR发生率,与Pax和ALT相比,ATG能更好的预防AR,改善移植肾功能,提高移植物早期(1年)存活率,并且不增加感染的发生风险.