Effect of basiliximab on renal allograft rejection within 1 year after transplantation

Basiliximab is widely used in clinical practice for initial immunosuppressive treatment of renal transplant recipients, seeking to reduce the incidence of acute rejection episodes without adverse events. This retrospective study included 123 renal allograft recipients transplanted at a single center. All were followed for longer than 1 year after transplantation and treated with calcineurin inhibitor and steroid (methylprednisolone) for prophylactic immunosuppression, but basiliximab and mycophenolate mofetil were optional. We compared the outcomes of renal transplant recipients who were versus treated were not with basiliximab as initial immunosuppressive therapy. Basiliximab was used for initial immunosuppression in 42 patients. Their maintenance immunosuppressive treatment included triple (n = 44) or double (n = 79) regimens, including a calcineurin inhibitor (cyclosporine [n = 87] or tacrolimus [n = 36]), methylprednisolone with or without mycophenolate mofetil. Twenty-six (21.1%) patients had a rejection episode within 1 year after transplantation and 22 (17.9%) had infections. Within the first year after transplantation the patients who were treated with basiliximab showed fewer rejection episodes (n = 6, 14.3%) than the patients without this therapy (n = 20, 24.7%), which was not statistically significant (P = .245). However, basiliximab significantly affected the occurrence of rejection episodes among the double immunosuppressive regimen group (P = .006), but not the triple regimen group (P = .098) without an impact on infection episodes (P value of double, triple = .291, .414) within 1 year after transplantation. We concluded that basiliximab was more useful for the recipients treated with double immunosuppression with a calcineurin inhibitor and steroid than for those on a triple regimen including mycophenolate mofetil.     

Alemtuzumab Induction and Prednisone-Free Maintenance Immunotherapy in Kidney Transplantation: Comparison with Basiliximab Induction—Long-Term Results

This study examined alemtuzumab (anti-CD 52, Campath-1H) and basiliximab (anti-CD 25, Simulect) as induction immunosuppression in kidney transplantation. We used a single-center, nonrandomized, retrospective, sequential study design to evaluate outcomes in kidney transplant recipients given either alemtuzumab (n = 123) or basiliximab (n = 155) induction in combination with a prednisone-free maintenance protocol using tacrolimus and mycophenolate mofetil. Kaplan-Meier analyses of long-term patient and graft survivals and rejection rates were determined according to induction agent, donor source and recipient ethnicity. Secondary endpoints included the quality of renal allograft function and the etiology of infectious complications. Overall long-term patient and graft survival rates did not significantly differ between patients treated with alemtuzumab and basiliximab. A lower rate of early (<3 months) rejection was observed in the alemtuzumab (4.1%) versus the basiliximab (11.6%) group, but the rates for both groups were equivalent at 1 year. Patient and kidney survival and rejection rates were nearly identical between Caucasians and African Americans that received alemtuzumab. Quality of renal function and incidence of infectious complications were similar in the two groups. Alemtuzumab induction therapy was similar in efficacy to basiliximab in a prednisone-free maintenance immunosuppressive protocol for an ethnically diverse population of kidney transplant recipients.     

Ethnic disparity in clinical outcome after heart transplantation is abrogated using tacrolimus and mycophenolate mofetil-based immunosuppression

BACKGROUND: Black American heart transplant recipients receiving cyclosporine-based primary immunoprophylaxis suffer higher rates of allograft rejection with hemodynamic compromise, infections, and posttransplant coronary artery disease. We examined the hypothesis that a combination of tacrolimus and mycophenolate mofetil "resurrects" clinical outcome of black Americans to those seen in white heart transplant recipients. METHODS: Sixty-three adult primary heart transplant recipients were included in this study. Twenty black American and 21 white patients who received tacrolimus-based primary immunoprophylaxis were enrolled in this prospective, observational parallel cohort investigation. A separate group of 22 black American patients were randomly allocated to receive cyclosporine-microemulsion-based primary prophylaxis and served as the control population for assessing outcomes in the black American group. Adjunctive immunosuppression included mycophenolate mofetil and corticosteroids. The primary end-point was the freedom from allograft rejection requiring treatment at 1 year. Secondary end-points included rejection with hemodynamic compromise, and patient or graft survival. Adverse events evaluated included development of infections requiring hospitalization and nonimmunological outcomes including hyperlipidemia, hypertension, and diabetes mellitus (new onset or worsened). RESULTS: Tacrolimus-treated black American patients had greater freedom from allograft rejection requiring treatment at 1 year than those treated with cyclosporine (64% vs. 37%, P=0.01). No differences were noted between tacrolimus-treated black Americans and whites in the primary end point (64% and 67% respectively, P=nonsignificant [NS]). Tacrolimus-based immunosuppression was associated with better 1-year survival in black Americans compared with cyclosporine (95% vs. 73%, P=0.04), and this end point was similar to that achieved in tacrolimus-treated white heart transplant recipients (95%). No differences in infection rates were noted among either group. Cyclosporine-treated black Americans suffered more hyperlipidemia and worse hypertension than tacrolimus-treated patients. CONCLUSIONS: Compared with cyclosporine, an immunosuppressive strategy using tacrolimus in black Americans achieves superior efficacy with regard to allograft rejection, higher allograft survival, and similar safety. Furthermore, tacrolimus-based immunosuppression is similar in immunological efficacy and safety in black Americans and in white heart transplant recipients.     

Steroid withdrawal or steroid avoidance in renal transplant recipients: focus on tacrolimus-based immunosuppressive regimens

Steroid-induced adverse effects after transplantation include cosmetic, metabolic, and cardiovascular complications. Steroid withdrawal or avoidance with cyclosporine-based regimens have been hampered by an unacceptably high rate of acute rejections and increased rates of graft loss. Recently the results of several large, randomized trials of steroid withdrawal/avoidance with tacrolimus-based immunosuppression in renal transplant recipients became available. A review of these trials appeared to be of clinical interest. Data from the THOMAS trial clearly indicate that steroid withdrawal from a regimen of tacrolimus, mycophenolate mofetil (MMF), steroids after 3 months after transplantation is safe with regard to acute rejection rate and graft survival. If an induction therapy with daclizumab is used in combination with tacrolimus and MMF (CARMEN trial), even steroid avoidance is safe with regard to acute rejection rate and graft survival. Finally, in the ATLAS trial, steroid avoidance with basiliximab in combination with tacrolimus (resulting in tacrolimus monotherapy) or alternatively with tacrolimus and MMF both resulted in similar graft survival, but higher rates of acute rejection. In conclusion, steroid withdrawal is safe from a triple-drug regimen of tacrolimus, MMF, and steroids after 3 months after transplantation, and steroid use may completely be avoided with tacrolimus, and MMF combined with daclizumab induction. Tacrolimus monotherapy may be achieved using basiliximab induction at the price of higher rates of acute rejection, but with unaffected graft survival. Thus tacrolimus-based immunosuppression with or without interleukin-2 receptor antagonist induction has made steroid withdrawal or avoidance a realistic option in renal transplantation.     

Immunosuppressive strategies to improve outcomes of kidney transplantation

The introduction of several immunosuppressive agents over the past decade has reduced the rate of acute rejection significantly and has improved short-term renal allograft survival. However, their impact on long-term outcomes remains unclear. Current immunosuppressive strategies are focused on improving long-term graft and patient survival along with maintaining allograft function. The approval of the new immunosuppressive agents: rabbit antithymocyte globulin, basiliximab, daclizumab, tacrolimus, mycophenolate, and sirolimus, also has facilitated the development of steroid- and calcineurin inhibitor-sparing regimens in kidney transplantation. We discuss the impact of various immunosuppressive regimens on the outcome measures of kidney transplantation: acute rejection episodes, allograft survival, and renal function.     

心脏移植后采用他克莫司替代环孢素A治疗的体会

目的 探讨心脏移植后因排斥反应或环孢素A(CsA)不良反应而将CsA替换为他克莫司(FK506)的临床效果.方法 6例原位心脏移植患者中,5例因发生严重排斥反应或排斥反应不能控制、1例因CsA的肝毒性,而将CsA替换为FK506,其它免疫抑制剂不变,转换时间为术后(167.8±166.7)d,FK506的用量为(6.0±1.4)mg/d,维持其血药浓度在(14.7±5.6) μg/L.心内膜心肌活检(EMB)联合超声心动图监测排斥反应.结果 随访(17.1±6.0)个月,6例患者全部存活,2例心功能下降者在换用FK506后心功能恢复正常.换用FK506前,排斥反应评分为(2.50±0.42)分,换用FK506后,排斥反应评分降至(0.60±0.39)分(P＜0.01).1例患者转换为FK506后3周,出现发热及胸腔积液,经抗结核治疗1周后好转,半年后停止抗结核治疗,患者至今存活1年;转换为FK506后,4例患者因血糖升高(其中2例转换前血糖即升高)需用胰岛素治疗;换用FK506后,CsA所致的多毛消失,牙龈增生减轻.结论 心脏移植后采用CsA进行免疫抑制治疗者,若反复发生排斥反应或出现不能耐受的CsA不良反应,可将CsA替换为FK506,临床效果明显.     

Induction immunosuppressive therapy in renal transplantation: does basiliximab make the difference?

The optimal prophylactic induction immunosuppressive therapy to prevent renal transplant rejection remains controversial. Recently, basiliximab efficiency has been reported in several studies. We sought to evaluate the efficiency of induction immunosuppressive therapy with basiliximab in renal transplantation in our unit based upon the acute rejection rate, patient and graft survivals, first hospital admission length, and incidence of infectious or malignant complications during 4 years of follow-up. We retrospectively evaluated the outcome of two groups of renal transplant recipients treated with triple immunosuppressive therapy (cyclosporine, mycophenolate mofetil, and prednisolone) without (group 1, 149 patients) or with (group 2, 104 patients) induction immunosuppression with basiliximab. The two groups did not differ in demographic characteristics, number of hypersensitized patients, cold ischemia time, or donor age. The group receiving basiliximab displayed a significantly lower acute rejection rate (7.6% vs 24%, P = .001) and shorter first hospital admission (14.4 +/- 8 vs 19.5 +/- 11 days). There was no difference in graft or patient survival, death due to sepsis, or incidence of posttransplant malignancies. Although there was no difference in graft or patient survival, immunosuppressive induction therapy with basiliximab yielded a significant reduction in the acute rejection rate.     

一剂赛尼哌对肾移植急性排斥反应的预防作用

目的 探讨1剂赛尼哌在预防同种异体肾移植急性排斥反应中的作用。方法 回顾性分析50例应用1剂赛尼哌的肾移植患者资料，同期30例未应用赛尼哌患者作为对照，随访6个月。分析比较2组患者急性排斥反应、移植肾功能、感染及赛尼哌不良反应发生情况。结果 赛尼哌组发生急性排斥反应13例（26％），对照组为17例（57％），差异有统计学意义（P〈0．05），2组患者药物不良作用方面、血液系统损害、肝功能损害、感染发生率及人／肾存活率差异无统计学意义（P〉0．05）。结论 联合应用1剂赛尼哌免疫抑制方案可以降低肾移植急性排斥反应发生率，改善移植肾功能，不良反应轻。     

Untreated rejection in 6-month protocol biopsies is not associated with fibrosis in serial biopsies or with loss of graft function

Donor age, calcineurin inhibitor nephrotoxicity, and acute rejection are the most significant predictors of chronic allograft nephropathy. Protocol biopsies, both in deceased- and living-donor renal grafts, have shown that cortical tubulointerstitial fibrosis correlates with graft survival and function. The impact of not treating subclinical acute rejection (SAR) is less clear. In this study, 126 de novo renal transplant recipients were randomly assigned to receive area-under-the-curve-controlled exposure of either a cyclosporine or a tacrolimus-based immunosuppressive regimen that included steroids, mycophenolate mofetil, and basiliximab induction. Protocol biopsies were taken before and 6 and 12 mo after transplantation. The prevalence of SAR was determined retrospectively. Fibrosis was evaluated by quantitative digital analysis of Sirius red staining in serial biopsies. Donor age correlated significantly with tubulointerstitial fibrosis in pretransplantation biopsies and inferior graft function at month 6 (rtau = -0.26; P = 0.033). Acute rejection incidence was 11.5%, and no clinical late rejection occurred. The prevalence of SAR at 6 mo was 30.8% but was not associated with differences in serial quantitative Sirius red staining at 6 or 12 mo, proteinuria, or progressive loss of GFR up to 2 yr. No differences were found in donor variables, histocompatibility, rejection history, or exposure of immunosuppressants. Controlled individualized calcineurin inhibitor exposure and subsequent tapering resulted in a low early acute rejection rate and prevented late acute rejection. Because, by design, we did not treat SAR, these results provide evidence that asymptomatic infiltrates in 6-mo surveillance biopsies may not be deleterious in the intermediate term. There is need for reliable biomarkers to prove that not all cell infiltrates are equivalent or that infiltrates may change with time.     

Tacrolimus versus cyclosporin in renal transplantation in Italy: cost-minimisation and cost-effectiveness analyses

BACKGROUND: The economic impact of therapies has increasingly become part of the clinical decision-making process. Costs associated with kidney transplantation are substantial and economic evaluations are useful in identifying immunosuppressive regimens that yield optimal clinical and economic benefits. METHODS: Utilisation of health care resources during the first 6-months after renal transplantation was examined in 557 kidney transplant recipients participating in a European, multicentre, randomised, parallel group study that compared the efficacy and safety of a tacrolimus-based regimen versus a cyclosporin-microemulsion-based regimen. Cost-minimisation and cost-effectiveness analyses were conducted from an Italian hospital perspective, including direct medical costs only (e.g. medication, hospitalisation). RESULTS: The incidence of acute rejection was significantly lower in the tacrolimus group than in the cyclosporin microemulsion (ME) group (32.5% versus 51.3%; p<0.001). Patient and graft survival were similar in both treatment groups. Renal transplant recipients receiving tacrolimus-based immunosuppression had lower utilisation of health care resources and lower total costs per patient than cyclosporin-ME treated patients. When surviving patients with a rejection-free graft were analysed, tacrolimus therapy was cost-saving, since it was both more effective (18.8% difference in the incidence of acute rejection; 95%CI 10.7%-26.8%; p<0.001) and less costly than cyclosporin-ME based therapy (cost difference euro9918). The costs per patient with a functioning graft were euro2305, the costs per surviving patient were euro1892 lower in tacrolimus treated patients. Sensitivity analyses using the key cost-drivers (hospitalisation, study drug, and concomitant medication) found the cost advantage of tacrolimus was maintained. CONCLUSION: In the first 6 months after renal transplantation, tacrolimus-based therapy was less costly than cyclosporin-ME based therapy. When surviving patients with a rejection-free graft were considered, tacrolimus was the dominant therapy.     

A Prospective, Randomized, Multicenter Trial of Tacrolimus-Based Therapy with or without Basiliximab in Pediatric Renal Transplantation

In a 6-month, multicenter, randomized, controlled, open-label, parallel-group trial, we investigated the efficacy and safety of adding basiliximab to a standard tacrolimus-based regimen in pediatric renal transplant recipients. Patients < 18 years received tacrolimus/azathioprine/steroids (TAS, n = 93) or tacrolimus/azathioprine/steroids/basiliximab (TAS + B, n = 99). Target tacrolimus levels were 10-20 ng/mL between days 0-21 and 5-15 ng/mL thereafter. Steroid dosing was identical in both groups. Basiliximab was administered at 10 mg (patients < 40 kg) or 20 mg (patients > or = 40 kg) within 4 h of reperfusion; the same dose was repeated on day 4. Biopsy-proven acute rejection rates were 20.4% (TAS) and 19.2% (TAS + B); steroid-resistant acute rejection rates were 3.2% and 3.0%, respectively. Patient survival was 100%; graft survival rates were 95% in both arms. The nature and incidence of adverse events were similar in both arms except toxic nephropathy and abdominal pain, which were significantly higher in the TAS + B arm (14.1% vs. 4.3%; p = 0.03 and 11.1% vs. 2.2%; p = 0.02; respectively). Median serum creatinine concentrations at 6 months were 86 micromol/L in the TAS and 91 micromol/L in the TAS + B arm; glomerular filtration rate was 79.4 and 77.6 (mL/min/1.73 m2), respectively. Adding basiliximab to a tacrolimus-based regimen is safe in pediatric patients, but does not improve clinical efficacy.     

Neoral rescue therapy in transplant patients with intolerance to tacrolimus

BACKGROUND: The calcineurin inhibitors, cyclosporine and tacrolimus, are the mainstay of current immunosuppressive regimens for the prevention of acute rejection in organ transplantation. The choice of the individual agent used often depends on the preference of the Transplant Center and patient type. Adverse effects associated with tacrolimus may impact its clinical utility in many patients. This study characterizes the clinical outcomes of transplant recipients who experienced adverse effects from tacrolimus and were converted to cyclosporine-microemulsion-based (Neoral([cyclosporine, USP] MODIFIED) therapy. METHODS: Hepatic or renal allograft recipients unable to maintain adequate immunosuppression with a tacrolimus-based regimen for reasons of toxicity or efficacy were recruited for this study and converted to cyclosporine-microemulsion-based therapy. Data were collected on drug dosing, trough concentrations, and treatment duration, as well as detailed information on tacrolimus-associated toxicities that prompted rescue with cyclosporine-microemulsion. Furthermore, clinical and laboratory data related to the clinical course of the patients after conversion to cyclosporine-microemulsion were recorded for up to 1 yr following conversion. RESULTS: One hundred and fifty-seven transplant recipients were enrolled in this study. Predominant reasons for discontinuation of tacrolimus were neurotoxicity (55%), diabetes (24%), nephrotoxicity (15%), and gastrointestinal intolerance (24%). Patients frequently had multiple symptoms prompting rescue therapy with cyclosporine-microemulsion. Over 70% of subjects had improvement or resolution of their tacrolimus-associated adverse symptoms within 3 months post-conversion. Acute rejection episodes occurred in 27% of patients converted to cyclosporine-microemulsion. CONCLUSIONS: Cyclosporine-microemulsion rescue therapy in patients experiencing adverse clinical effects associated with tacrolimus is an effective treatment option which leads to resolution of these adverse effects in the majority of patients, and allows for satisfactory clinical outcomes.     

Multicenter, randomized study of the use of everolimus with tacrolimus after renal transplantation demonstrates its effectiveness

BACKGROUND: Clinical data are lacking concerning concomitant administration of everolimus and tacrolimus in renal transplant recipients. METHODS: In a prospective, multicenter, open-label, exploratory, randomized, 6-month study, 92 de novo renal transplant patients received everolimus, steroids, and basiliximab with low or standard tacrolimus exposure. The primary objective was to compare renal function at 6 months after transplant. RESULTS: Mean 6-month serum creatinine (primary safety variable) was 112+/-31 micromol/L (1.26+/-0.35 mg/dL) and 127+/-50 micromol/L (1.44+/-0.57 mg/dL) in the low and standard tacrolimus groups, respectively, (n.s.); mean estimated GFR (Nankivell) was 75.3+/-16.6 mL/min and 72.5+/-15.2 mL/min (n.s.). Biopsy-proven acute rejection occurred in 13 patients: seven (14%) in the low tacrolimus group and six (14%) in the standard tacrolimus group, n.s. One graft was lost in the standard tacrolimus group. No patients died. CONCLUSIONS: Tacrolimus exposure reduction in the presence of everolimus, steroids and basiliximab induction results in good efficacy in de novo renal transplant recipients with very well-preserved renal function. Additional studies are warranted because between-group comparisons were limited by the relatively small differences in tacrolimus exposure in the 2 arms; trough levels were toward the upper end of the low-exposure ranges and toward the bottom of the standard-exposure ranges.     

Basiliximab in association with tacrolimus and steroids in caucasian cadaveric renal transplanted patients: significant decrease in early acute rejection rate and hospitalization time

Safety and tolerability of basiliximab in renal transplantation have been proven in different immunosuppressive regimens. Few informations are available about the association of basiliximab with tacrolimus and steroids. We present a retrospective analysis performed in Caucasian cadaveric renal transplant recipients, comparing a basiliximab, tacrolimus and steroids induction protocol (GrA: 51 patients) with a tacrolimus and steroids protocol (GrB: 46 patients). A significant decrease in acute rejection rate in the first 3 months (2.0% vs. 17.4%; p < 0.01) was noted. Interestingly, the recipients in GrA were at major immunologic risk for the younger age of recipients, the greater number of mismatches and the higher rate of second transplants. The hospitalization times resulted reduced of 5.3 d in GrA vs. GrB (20.8 d vs. 26.1 d; p < 0.05). The adverse events patterns and profiles were similar in the two treatments groups. One patient in each group had a post-transplant lymphoprolipherative disorder. No significant difference was found in patient and graft survival. According to the results of this study, in a Caucasian adult population, basiliximab in association with tacrolimus and steroids is a safe and efficacious tool for acute rejection prevention and it is cost saving by reducing the hospitalization times.     

Use of Basiliximab Induction in Low–Immunological Risk Renal Transplant Recipients Receiving Tacrolimus-Based Immunosuppression

Basiliximab induction treatment has been shown to reduce the incidence of acute rejection episodes without the secondary side effects observed with antilymphocyte polyclonal antibodies. We analyzed our experience with basiliximab induction associated with tacrolimus-based immunosuppression among low–immunological risk renal transplant recipients. We retrospectively analyzed 55 renal transplantation patients of low inmunological risk who received organs from donors younger than 55 years. We compared a group of 21 patients (38.9%; group 1) treated with basiliximab (Simulect, Novartis, Basel, Switzerland) with 33 patients (61.1%; group 2) without induction. The patient groups did not differ in recipient age (46.39 ± 11.1 in group 1 vs 41.82 ± 11.02 years in group 2; P = .25), donor age (36.71 ± 14.72 vs 35.09 ± 14.63 years; P = .69), or recipient and donor gender. No differences were observed in dose or tacrolimus levels during follow-up. The incidences of delayed graft function (DGF; 28.6% vs 28.1%; P = .97) and of acute rejection episodes (9.5% vs 15.6%; P = .52) were similar in both groups. Serum creatinine and proteinuria levels (P > .05) and hospital admissions due to infections (36.4 vs 35.7%; P = .97) were also similar in both groups. At 1 year graft survival rates were 92% and 96% (P = .97) in groups 1 and 2, respectively. Considering our findings and the costs of basiliximab treatment, we conclude that routine administration of basiliximab cannot be justified in young, low–immunological risk transplant recipients undergoing tacrolimus-based immunosuppression.     

Impaired erythropoietin production in liver transplant recipients: the role of calcineurin inhibitors.

Anemia is common following liver transplantation. Because cyclosporine inhibits erythropoietin (Epo) production in experimental models, we investigated whether Epo production was impaired in liver transplant recipients receiving a cyclosporine- or tacrolimus-based immunosuppressive regimen. First, serum Epo levels were measured before and 1 year after transplantation in 35 liver transplant recipients. Second, serum Epo levels were compared in a large series of liver transplant recipients with stable graft and renal functions: 27 receiving a cyclosporine-based and 31 receiving a tacrolimus-based immunosuppressive regimen. A reference group was made up of 22 blood donors and 21 nontransplanted subjects with iron-deficiency anemia. Serum Epo levels were significantly lower after than before liver transplantation, especially in cyclosporine-treated patients. Serum Epo concentrations correlated with hematocrit values in both transplant recipients and control subjects. Using multiple linear regression models, the polynomial relationship between hematocrit and serum Epo values was similar to the control group in patients under tacrolimus, whereas Epo production was significantly reduced in patients under cyclosporine-based immunosuppression. Hematocrit values and the type of calcineurin inhibitor were the only parameters independently related to Epo levels. In conclusion, cyclosporine, but not tacrolimus, inhibits Epo production at the doses used in clinical practice.     

Efficacy and safety of basiliximab with a tacrolimus-based regimen in liver transplant recipients

BACKGROUND: Induction with monoclonal antibodies for prevention of acute cellular rejection (ACR) may avoid many of the adverse events associated with polyclonal antibodies. Basiliximab, a chimeric monoclonal antibody directed against the alpha-chain of the interleukin 2 receptor (CD25), has been extensively evaluated as an induction therapy for kidney transplant recipients, more frequently in combination with a cyclosporine-based regimen. In this study, we assessed the efficacy and safety of basiliximab in combination with a tacrolimus-based regimen after liver transplantation. METHODS: Fifty consecutive liver transplants (47 cadaveric donors; 3 living donors) were analyzed. All patients received two 20-mg doses of basiliximab (days 0 and 4 after transplantation) followed by tacrolimus (0.15 mg/kg/day; 10-15 ng/mL target trough levels) and a tapered dose regimen of steroids. Follow-up ranged from 404 to 1,364 days after transplantation (mean 799.89 days, SD+/-257.37; median 796 days). RESULTS: A total of 88% of patients remained rejection-free during follow-up with an actuarial rejection-free probability of 75% within 3 months. The actuarial patient survival rate at 3 years was 88%, and the graft survival rate was 75%. Twelve (24%) patients experienced one episode of sepsis, requiring temporary reduction of immunosuppressive therapy. There were no immediate side effects associated with basiliximab and no evidence of cytomegalovirus infection or posttransplant lymphoproliferative disorder. CONCLUSIONS: Basiliximab in combination with a tacrolimus-based immunosuppressive regimen is effective in reducing episodes of ACR and increasing ACR-free survival after liver transplantation. In addition, basiliximab does not increase the incidence of adverse effects or infections.     

Randomized clinical trial of the effect of microemulsion cyclosporin and tacrolimus on renal allograft fibrosis

BACKGROUND: The aim of this study was to compare the effect of Neoral cyclosporin- and tacrolimus-based therapy on the development of renal allograft fibrosis (chronic allograft nephropathy; CAN) in a prospective randomized trial. METHODS: A total of 102 patients undergoing renal transplantation were randomized to immunosuppression with either microemulsion cyclosporin (Neoral; 15 mg per kg per day adjusted to whole-blood trough concentrations of 200-300 ng/ml) or tacrolimus (0.2 mg per kg per day adjusted to whole-blood trough levels of 8-15 ng/ml) in conjunction with steroids, or at a lower dose (7 mg per kg per day and 0.1 mg per kg per day respectively) with the addition of azathioprine for non-heart-beating renal transplant recipients. Renal transplant interstitial fibrosis was quantified using computerized histomorphometric measurement of picrosirius red-stained 1-year protocol renal transplant biopsies. Levels of interstitial fibrosis were compared in relation to observed efficacy and toxicity profiles of the two drugs. RESULTS: There was a significant increase in allograft interstitial fibrosis in the patients treated with Neoral compared with those given tacrolimus. There was no significant difference in the demographic characteristics between the patient groups or in the incidence of acute rejection (Neoral 36 per cent versus tacrolimus 35 per cent) or steroid-resistant rejection (both 10 per cent) between the two drugs. There was a higher incidence of insulin resistance in the tacrolimus group (post-transplant diabetes mellitus, glucose tolerance testing) but this was not statistically significant. Neoral was associated with a significant increase in total cholesterol (P = 0.030) and low-density lipoprotein (P = 0.021) levels, which persisted throughout the study period. CONCLUSION: Despite equivalent efficacy and pretransplantation risk factors for CAN, Neoral was associated with increased allograft fibrosis and significantly higher serum low-density lipoprotein cholesterol levels compared with tacrolimus.     

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.     

Basiliximab induction in patients receiving tacrolimus-based immunosuppressive regimens

Purpose

The use of basiliximab induction increased significantly in recent years based on its superior efficacy and excellent safety profile demonstrated in studies with cyclosporine-based immunosuppression. However, its clinical utility in patients receiving tacrolimus-based immunosuppressive regimens is still uncertain.

Methods

We retrospectively reviewed data of 366 low immunological risk recipients of deceased donor kidney transplants. Of them, 134 received basiliximab and tacrolimus (TAC-IL2-RA), 100 received basiliximab and delayed tacrolimus(dTAC-IL2-RA), and 132 patients received tacrolimus without basiliximab(TAC-No). The endpoints were the incidence of acute rejection, graft function, and patient and graft survivals at 1 year.

Results

The incidence of acute rejection was higher in dTAC-IL2-RA compared to TAC-IL-2RA and TAC-No Groups (33 vs.14.9 vs. 14.3 %, p < 0.001). Inferior creatinine clearance was observed in dTAC-IL2-RA Group compared to TAC-IL2-RA and TAC-No Groups at months 1 (41.6 vs. 49.9 vs. 44.8 mL/min, p = 0.004), 3 (49.8 vs. 57.2 vs. 53.5 mL/min, p = 0.017), and 6 (53.1 vs. 61.8 vs. 57.0 mL/min, p = 0.001). Patients who received basiliximab (TAC-IL2-RA and dTAC-IL2-RA Groups) had lower incidence of posttransplant diabetes (24 vs.18 vs. 39.3 %, p = 0.009). Patient and graft survivals were similar among the groups.

Conclusions

In low immunological risk kidney transplant recipients receiving tacrolimus, the use of basiliximab induction was not associated with lower rejection rates and did not allow delayed tacrolimus introduction.