The interleukin-2 receptor antagonist basiliximab has proven in large clinical trials to be safe and effective to reduce acute rejections in the first year after renal transplantation. Since acute rejections are a risk factor for chronic graft loss, their effective reduction might have a positive effect on long term allograft survival. So far data is spares to prove this hypothesis and 10-year follow up on basiliximab induction therapy is not available. In our center, 41 patients were enrolled in the multicenter trial CHIB201 in 1995/96 comparing basiliximab vs no induction therapy after renal transplantation. We retrospectively analyzed the outcome of these patients after 10 years. The main reason for patient death with functioning graft were infectious complications (basiliximab: 3/20, placebo 1/19), 21% of all patients developed cancer without an obvious correlation to specific immunosuppression. Death censored 10-year graft survival was equivalent in both groups: 65% in the basiliximab and 68% in the placebo group with a mean s-creatinine-clearance of 60 and 44 ml/min. In this small study patient and graft survival was equivalent 10 years after transplantation comparing basiliximab induction therapy and placebo.

BACKGROUND:

Several randomized clinical trials performed on adult renal transplant recipients have shown a significant reduction in the incidence of acute rejection by using basiliximab as induction therapy. However, few studies have been conducted on kidney graft survival following the use of the drug among pediatric transplant recipients.

OBJECTIVE:

To address the efficacy and safety of basiliximab in the improvement of the survival of children with kidney transplants.

METHODS:

This randomized, double-blind single-center clinical trial was conducted on 28 children (57% male) who underwent live-unrelated renal transplantation. They were randomly assigned into an intervention group receiving basiliximab (10 mg in patients weighing <40 kg or 20 mg in patients ≥40 kg) as induction therapy in combination with the standard immunosuppressive regimen (n=14), or to the control group (n=14) receiving only the standard immunosuppressive regimen (without basiliximab). The outcome was assessed by the measurement of serum creatinine level before transplantation, and 24, 48, and 72 hours as well as 3, 6, and 12 months post-transplantation. The estimated glomerular filtration rate at 12 months post-transplantation and graft survival were also measured. The number of acute rejection episodes in transplant recipients was also considered.

RESULTS:

The mean±SD age of participants was 12.3±4.2 years. No difference was observed between the two groups in terms of serum creatinine level before and after transplantation at various time points. The mean±SD eGFR at 12 months post-transplantation was 87.8±8.4 in the basiliximab and 85.2±5.8 in the control group (p=0.37). No significant difference was observed between the two groups in terms of acute rejection episodes (25% in basiliximab and 33% in the control group). The graft survival at 1-year post-transplantation was 93% in the basiliximab and 86% in the control group (p=0.54).

CONCLUSION:

Adding basiliximab to the standard immunosuppressive regimen may not improve the graft survival.

The chimeric, monoclonal antibody basiliximab inhibits the proliferation and clonal expansion of activated T cells. To date basiliximab has been used only in combination with other immunosuppressive agents for rejection prophylaxis after solid organ transplantation. An infant underwent liver transplantion (LTx) at the age of 5 months because of biliary atresia. The primary immunosuppression consisted of cyclosporine and prednisolone. As a result of a steroid resistant rejection episode on day 26 post-LTx we had to switch the initial immunosuppressive regiment to tacrolimus and steroids. Because of severe cholestasis and assumed impaired enteral resorption we were forced to administer an unusually high dosage (2 mg/kg/day) of tacrolimus. Four months after LTx an intestinal B-cell lymphoma was diagnosed when the patient suffered from a small bowel perforation. After stopping the immunosuppressive medication we started treatment with the anti-CD20 monoclonal antibody rituximab for B-cell depletion. During the 12 wk no B cells were detectable in the peripheral blood by flow cytometry. In this setting we started a monotherapy with repetitive doses of basiliximab for immunosuppression. During the following course there was no further rejection and no recurrence of the tumor. From this experience we conclude that monotherapy with basiliximab after LTx and anti-CD20 treatment for B-cell lymphoma is efficient and safe.

Background Calcineurin inhibitors reduce short-term kidney transplant failure, but may contribute to late transplant loss. The role of alemtuzumab (a potent lymphocyte-depleting antibody) as induction therapy followed by an early reduction in CNI exposure after kidney transplantation is uncertain. The 3C Study aims to assess the efficacy and safety of alemtuzumab (followed by low-dose CNI) compared to basiliximab (with standard dose CNI) among patients receiving kidney transplants. Methods This randomized trial included 852 patients scheduled to receive a kidney transplant who were randomly assigned alemtuzumab-based induction therapy (followed by low-dose tacrolimus and mycophenolate) or basiliximab-based induction therapy (followed by standard-dose tacrolimus, mycophenolate and steroids). The primary outcome is biopsy-proven acute rejection at 6 months. Key secondary outcomes include delayed graft function, steroid resistant rejection, transplant survival, serious infections (defined as opportunistic infections or infection requiring hospitalisation) and cause-specific mortality. Tertiary outcomes include the incidence of the primary outcome in different types of transplant recipient. Results 426 participants were assigned alemtuzumab and 426 to basiliximab. Average age was 51 years and 65% were male. Approximately one-third of transplants followed each of donation after brain death, donation after cardiac death and living donation. During the first 6 months of follow-up, about 100 participants had biopsy-proven acute rejection, about 30 transplants failed and over 250 participants had a serious infection. Conclusion The 3C Study is the largest randomized trial to assess the clinical efficacy and safety of alemtuzumab-based induction in kidney transplantation and the unblinded clinical efficacy results would be presented for the first time during the WTC meeting. With about 100 rejection episodes and 250 serious infections, the study has excellent statistical power to detect clinically important treatment effects. These results should have an important impact on the choice of induction therapy at the time of kidney transplantation.

This study aims to study the effects that two standard of care immunosuppression induction regimens have on regulatory T cells (Treg) in live donor renal transplant recipients. Both regimens are currently used in this hospital for early immunosuppression induction but the effects on Treg numbers and function is not well understood and likely will impact long term immune function.

The number of acute rejections and infections after pediatric kidney transplantation (KTX) could not be reduced in the last years. To reduce these events, we investigated a new immunosuppressive protocol in a prospective trial. After KTX, 20 children (median age 12 years, range 1-17) were initially treated with Basiliximab, ciclosporine A (CsA) (trough-level = C0 200-250 ng/mL) and prednisolone. After 2 weeks, CsA dose was reduced to 50% (C0 75-100 ng/mL, after 6 months: 50-75 ng/mL) and everolimus (1.6 mg/m2/day) was started (C0 3-6 ng/mL). Six months after KTX prednisolone was set to alternate dose and stopped 3 months later. All 20 protocol biopsies 6 months after KTX showed no acute rejection or borderline findings. Indication biopsies resulted in no acute rejections and two borderline findings. Mean glomerular filtration rate (GFR) 1 year after KTX was 71 ± 25 mL/min/1.73 m2. Without cytomegalovirus (CMV)-prophylaxis, only two primary CMV infections were seen despite a donor/recipient-CMV-constellation pos./neg. in 10/20 children. In pediatric KTX, de novo immunosuppression with low-dose CsA, everolimus and steroid withdrawal after 9 months led to promising results according to numbers of acute rejections and infections. Further follow up is needed. Future larger trials will have to confirm our findings. © 2010 The American Society of Transplantation and the American Society of Transplant Surgeons.

A total of 192 children and adolescents undergoing renal transplantation were randomly chosen to receive tacrolimus, azathioprine and corticosteroids (TAS,n =93) or tacrolimus, azathioprine, corticosteroids and two doses of basiliximab (TAS + B, n=99). Six-month outcome data have previously been reported; this manuscript reports the 2-year data. Complete 2-year data were available on 164 (85.4%) of the original 192 patients. There was a single death in the TAS arm. Kaplan-Meier estimates of survival free of graft loss at 2 years were 94.9% in the TAS + B arm and 89.6% in the TAS arm [hazard ratio (HR) 0.52; 95% confidence interval (CI) 0.17 to 1.54, P=0.23]. Estimates of survival free from rejection at 2 years were 75.2% in the TAS + B arm and 68.7% in the TAS arm (HR 0.81; 95% CI 0.46 to 1.40, P=0.44). The mean estimated glomerular filtration rate (GFR) at 2 years, was 65.8 ml/min per 1.73 m2 body surface area in the TAS arm and 66.7 ml/min per 1.73 m2 in the TAS + B arm (P=0.78). Blood pressure and cholesterol levels were similar in the two arms, and there was no evidence of a difference in the incidence of infection or malignancy. These data provide further evidence of a lack of benefit associated with the addition of basiliximab to a TAS regimen for European paediatric renal transplant recipients at low immunological risk. © IPNA 2008.

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