Randomized double-blind study of immunoprophylaxis with basiliximab,a chimeric anti-interleukin-2 receptor monoclonal antibody,in combination with mycophenolate mofetil-containing triple therapy in renal transplantation

BACKGROUND: Acute rejection remains a major problem in renal transplantation. Immunoprophylaxis with basiliximab (Simulect) has achieved significant reductions in acute rejection episodes in renal allograft recipients receiving dual immunosuppression. This study explored the tolerability and cumulative benefit of combining basiliximab with triple-drug therapy-cyclosporine (USP Modified, Neoral), mycophenolate mofetil, and steroids. METHODS: In a randomized, double-blind, placebo-controlled, multicenter study, 123 kidney transplant recipients received either basiliximab at 20 mg before transplantation (day 0) and 20 mg on day 4 (n=59), or placebo (n=64). All received triple-drug immunosuppression and were followed for 6 months. RESULTS: Tolerability of basiliximab was equivalent to placebo, with no increase in serious adverse events, infection, malignancy, or posttransplant lymphoproliferative disorder. At 6 months, there were trends in favor of basiliximab over placebo in the incidences of first biopsy-confirmed acute rejection (15.3% vs. 26.6%, P=NS) and of acute rejection treated with antibody (5.1% vs. 15.6%, P=NS). Kaplan-Meier estimates at 4 weeks and 6 months were significantly in favor of basiliximab treatment for first acute rejection, biopsy-confirmed rejection, rejection episodes treated with antibody therapy, and treatment failure. Renal function improved more rapidly in the basiliximab group, with mean creatinine clearance at week 2 being 54.7 mL/min versus 43.2 mL/min for placebo (P=0.034). At 12 months, patient survival was 100% in both groups; graft survival was 94.9% with basiliximab and 92.2% with placebo. CONCLUSIONS: Basiliximab immunoprophylaxis is safe, well tolerated, and shows a trend toward reduction in number of acute rejection episodes in renal transplant patients receiving cyclosporine, mycophenolate mofetil, and steroids.     

Sirolimus in kidney transplantation from marginal donors

Nephrotoxicity caused by calcineurin inhibitors can lead to either delayed graft function or long-term decline of renal function after kidney transplantation. Therefore, recipients of renal transplants from marginal donors require non-nephrotoxic immunosuppression. Eighteen patients received kidney transplants from marginal donors, with a calcineurin inhibitor-free immunosuppressive regimen, based on basiliximab, mycophenolate mofetil, steroids, and sirolimus. Renal graft biopsy was performed in all cases before surgery. Mean follow-up was 11.8 months. We report immediate renal function in 9 patients, delayed graft function in 5 and acute tubular necrosis in 4 patients. One patient was successfully treated for biopsy-proven acute rejection. Hypercholesterolemia and hypertriglyceridemia were the most common adverse effects (n = 13) associated with arthralgia (n = 2) and thrombocytopenia (n = 2). Five patients underwent a switch to tacrolimus, due to sirolimus-induced side effects. Immunosuppression without the use of calcineurin inhibitors is a safe and effective regimen in kidney transplantation, although sirolimus-related side effects still represent a morbidity factor in these patients.     

Basiliximab versus daclizumab combined with triple immunosuppression in deceased donor renal graft recipients

In this prospective, randomized, open-label, single-center study, we compared the efficacy and safety of two anti-interleukin-2 receptor monoclonal antibodies among adult recipients of at least 1 HLA-mismatched deceased donor renal grafts. Eligible patients were randomized to induction with either basiliximab or daclizumab. Both groups received cyclosporine microemulsion (CsA Neoral), mycophenolate mofetil, and methylprednisolone. An intent-to-treat analysis of 1-year data assessed the incidence of acute rejection episodes, the renal graft function, the safety, and the patient and graft survivals. Among 127 patients, six (10.0%) and seven (11.5%) patients experienced biopsy-confirmed acute rejection at 12 months, in the basiliximab and the daclizumab groups, respectively. Two renal grafts were lost in the basiliximab and six in the daclizumab cohort, one of them due to rejection. One basiliximab and two daclizumab patients died. Hospital treatment was required for 25 and 33 infections in basiliximab and daclizumab groups, respectively. One basal cell carcinoma of skin was detected. One hypersensitivity reaction was observed with daclizumab. At 12 months, serum creatinine was 101+/-28 micromol/L with basiliximab and 109+/-41 micromol/L with daclizumab. Patient survival was 98.4% with basiliximab and 96.7% with daclizumab, and graft survival was 96.8% versus 90.8%, respectively. No significant differences were observed between the groups. Basiliximab or daclizumab combined with triple therapy was an efficient and safe immunosuppression strategy, demonstrated with low incidence of acute rejection episodes, an acceptable adverse event profile, excellent graft function, and high survival rates in adult recipients within the first year after deceased donor renal transplantation.     

Effective immunoprophylaxis with basiliximab plus triple therapy in renal transplantation: five-year single-center experience

We studied prospectively the efficacy and safety of basiliximab combined with triple immunosuppression in adult recipients of > or = 1 HLA-mismatched deceased donor renal grafts. All studied patients received equal immunosuppressive drugs: 20 mg infusion of basiliximab on day 0 and on day 4, cyclosporine microemulsion (Neoral), mycophenolate mofetil, and methylprednisolone. An analysis of 1-year data assessed the incidence of acute rejection episodes, safety of this therapy, renal graft function, and patient and graft survivals. One hundred seventy-two patients were studied. The HLA-antigen mismatches were 2.9 +/- 0.9 (mean +/- SD), and the cold ischemia time was 22.0 +/- 7.5 hours. Fifty-three (31.5%) patients experienced delayed graft function. At 12 months, 5 (3.0%) patients experienced acute rejection. Six renal grafts were lost, but not from rejection. Two patients died. Sixty-six infections required treatment in the hospital. One carcinoma of cervix (in situ) and two basal cell carcinomas of skin were detected. Hypersensitivity reactions and cytokine-release syndrome were not observed. At 12 months, serum creatinine was significantly higher (119 +/- 46 micromol/L; P < .001) in patients with delayed graft function than in patients with immediate graft function (99 +/- 26 micromol/L). Patient and graft survivals were 98.8% and 97.1%, respectively. Basiliximab combined with this triple therapy was an efficient and safe immunosuppression strategy, demonstrated with very low incidence of acute rejections, an acceptable adverse event profile, excellent graft function, and high short-term survival rates in adult recipients of deceased donor renal transplant.     

Comparative study of the cellular pharmacodynamics of tacrolimus in renal transplant recipients treated with and without basiliximab

Basiliximab is a recently developed immunosuppressive agent for the prevention of acute allograft rejection in renal transplant recipients. The combination use of basiliximab and a calcineurin inhibitor was suggested to be more effective in comparison to immunosuppressive therapy using calcineurin inhibitor without basiliximab. Cyclosporine has been generally administered with basiliximab for renal transplant recipients. However, in cases of tacrolimus-based immunosuppressive regimen, the clinical efficacy and safety of combined use of tacrolimus and basiliximab remains to be elucidated. This study evaluated the tacrolimus pharmacological efficacy using a lymphocyte immunosuppressant sensitivity test (LIST) with MTT assay procedures in 16 cases of renal transplant recipients treated by tacrolimus without basiliximab and in 13 cases treated by tacrolimus in combination with basiliximab. The rate of acute rejection episodes in the recipients treated with tacrolimus plus basiliximab was 1/13 (7.7%), whereas the rate in the recipients treated with tacrolimus without basiliximab was 6/16 (37.5%). The recipients were divided into two groups according to their peripheral blood mononuclear cell (PBMC) sensitivity to tacrolimus [i.e., including a tacrolimus high sensitivity group (IC(50) <1.0 ng/ml) and a low sensitivity group (IC(50) >1.0 ng/ml). In the recipients treated with tacrolimus without basiliximab, the rate of acute rejection episodes in the tacrolimus high sensitivity group was 1/10 (10.0%), which was significantly lower than the rate in the low sensitivity group of 5/6 (83.3%; p = 0.008). The incidence of cytomegalovirus infection was not significantly different between the tacrolimus high and the low sensitivity groups of the recipients treated with tacrolimus with and without basiliximab. Therefore, in the case of selected tacrolimus-based immunosuppressive therapy for renal transplant recipients, the tacrolimus pharmacological efficacy should be evaluated using LIST at a time just before the transplant procedure in order to accurately predict allograft rejection. The data also suggested that low tacrolimus sensitivity recipients should be treated with tacrolimus-based immunosuppressive therapy in combination with basiliximab.     

Multicenter Randomized Prospective Trial of Steroid Withdrawal in Renal Transplant Recipients Receiving Basiliximab, Cyclosporine Microemulsion and Mycophenolate Mofetil

Corticosteroids withdrawal from immunosuppressive regimens has thus far been associated with increased risk of acute rejection episodes. In this study, basiliximab, a chimeric monoclonal interleukin-2 receptor antagonist, added to a maintenance regimen consisting of cyclosporine microemulsion and mycophenolate mofetil was studied for its effectiveness in allowing early corticosteroid withdrawal in de novo renal allograft recipients. Primary renal transplant recipients receiving basiliximab, cyclosporine-microemulsion, and mycophenolate mofetil, were randomized to either corticosteroid withdrawal at day four post-transplantation (n = 40) or standard steroid therapy (n = 43). The primary endpoint was the incidence of biopsy-proven acute rejection episodes. Randomized subjects who underwent transplantation and received at least one dose of basiliximab were analyzed in an intent-to-treat fashion. The incidence of biopsy-proven acute rejection at 12 months was not significantly different between the steroid withdrawal group (20%) and the standard treatment group (16%). Patient and graft survival was 100% in the steroid withdrawal group while one death in a patient with a functioning graft occurred in the standard steroid group. Seventy-two percent of the steroid withdrawal group remained off steroids at 6 months post-transplant. Allograft function and incidence of adverse events and infections were similar between the two groups. Rapid and early corticosteroid withdrawal among renal transplant recipients receiving basiliximab induction and daily therapy with cyclosporine-microemulsion and mycophenolate mofetil was not associated with an increased risk of acute rejection.     

HLA mismatches remain risk factors for acute kidney allograft rejection in patients receiving quadruple immunosuppression with anti-interleukin-2 receptor antibodies

BACKGROUND: New immunosuppressive drugs such as anti-interleukin-2 receptor antibodies (aIL2R) and mycophenolate mofetil (MMF) have reduced the incidence of acute rejection after renal transplantation. Whether matching donor and recipient human leukocyte antigen (HLA) antigens is still relevant in patients receiving modern immunosuppression has been questioned. METHODS: We retrospectively analyzed the incidence and risk factors of acute rejection during the first posttransplant year and the impact of acute rejection on long-term graft survival in a cohort of 208 renal transplant patients treated with aIL2R (basiliximab, n=166; daclizumab, n=42), calcineurin inhibitors (tacrolimus, n=180; cyclosporin, n=28), mycophenolate mofetil, and steroids. Graft and patient survival were calculated by the Kaplan-Meier method. Risk factors for acute rejection were analyzed by logistic regression modeling. RESULTS: Twenty-seven patients were treated for acute rejection (26 biopsy-proven) during the first posttransplant year. The Kaplan-Meier estimate of first-year acute rejection was 13.2%. The number of HLA mismatches (odds ratio [OR] 1.65 per HLA mismatch) and long periods of dialysis before transplantation (OR 3.1 for more than 4 years of dialysis) were the only independent risk factors for first-year acute rejection. First-year acute rejection was associated with a significant reduction in overall and death-censored graft survival at 5 years after transplantation. CONCLUSIONS: Although infrequent in patients receiving modern immunosuppressive drugs, acute rejection remains an important risk factor for graft loss after renal transplantation. Our results suggest that better HLA matching and shorter periods of dialysis before transplantation could reduce acute rejection rates and further improve outcomes under current immunosuppressive regimens.     

A novel approach to successful ABO-incompatible high-titer renal transplantation

BACKGROUND: Currently the long-term outcome among recipients of ABO-incompatible renal transplantations is excellent in Japan. However, previous reports have documented poor outcomes in patients with high (> 1:256) anti-A/B antibody titers pretreatment. The immunosuppressive protocol for ABO-incompatible high-titer renal transplantation has remained a medical challenge. METHODS: We treated 3 patients with high (> 1:512) anti-A/B antibody titers prior to ABO-incompatible renal transplantation. Our immunosuppressive protocol was initiated 1 month prior to surgery and included mycophenolate mofetil (1 g/d) and low-dose steroid (methylprednisolone [8 mg/d]). Two doses of the anti-CD20 antibody rituximab, (150 mg/m(2)) were administered 2 weeks before and on the day of transplantation. We performed antibody removal with 6 to 8 sessions of plasmapheresis (plasma exchange or double-filtration plasmapheresis) before transplantation. Splenectomy was also performed on the day of transplantation. Postoperative immunosuppression followed the same regimen as ABO-compatible cases, in which calcineurin inhibitors were initiated 3 days before transplantation combined with 2 doses of basiliximab. RESULT: With this protocol, the anti-A/B antibody was reduced to below 1:16 in all cases. All 3 patients underwent successful transplantation with a mean current serum creatinine of 1.32 mg/dL (range, 1.22-1.50 mg/dL). There were no episodes of antibody-mediated rejection. No serious complications or side effects were encountered. CONCLUSIONS: A preconditioning protocol consisting of rituximab infusions, splenectomy, plasmapheresis, and pharmacologic immunosuppression enabled ABO-incompatible renal transplantation in patients with high (> 1:512) anti-A/B antibody titer.     

Cyclosporine-sparing effect of basiliximab in renal transplant recipients with mycophenolate mofetil

Basiliximab added to a maintenance regimen consisting of cyclosporine microemulsion and mycophenolate mofetil was studied for its effectiveness in allowing early steroid withdrawal in renal transplantation. Furthermore, the cyclosporine-sparing effects between groups with and without basiliximab induction therapy were compared. PATIENTS: Between September 2001 and June 2003, 90 patients underwent renal transplants with cyclosporine-based immunosuppression, namely, cyclosporine, mycophenolate mofetil, and methylprednisolone, (group 1; n = 25). During the latter half of the study basiliximab was administered during the induction phase (group 2; n = 65). In group 2, steroids were completely withdrawn on postoperative day 14 in 57 patients. RESULTS: The incidence of acute rejection was significantly higher among group 1 patients (P = .005). The incidence of steroid-resistant rejection in group 1 patients was significantly higher (P = .025). At each time point cyclosporine levels in group 1 patients were significantly higher (P < .01). The incidence of infection was comparable between the groups. Patient and graft survival rates in group 1 were 100% and 100%; in group 2, they were 99% and 99%, respectively. In group 2, steroids were discontinued in 57 patients with permanent withdrawal achieved in 32 patients (56%). CONCLUSION: The use of basiliximab, together with mycophenolate mofetil allowed for a significant reduction in the cyclosporine dose without increasing the risk of acute rejection. Although further follow-up is necessary to confirm the effect, this regimen may attenuate cyclosporine nephrotoxicity thereby affecting the long-term outcomes of renal transplantation.     

Influence of methylprednisolone on plasma homocysteine levels in cadaveric renal transplant recipients

The aim of the present study was to investigate plasma homocysteine levels in renal transplant recipients in the course of steroid-based or steroid-free immunosuppression. Data from 32 patients were retrospectively analyzed according to the steroid immunosuppressive regimen. The 20 recipients on methylprednisolone (MP) plus cyclosporine (CyA) or tacrolimus (TRL) (n = 20) showed similar creatinine levels when compared with those on calcineurin inhibitors plus mycophenolate mofetil (MMF; n = 12), (1.6 +/- 1.5 vs 1.6 +/- 0.4 mg/dL; P = NS) but significantly higher total plasma homocysteine (tHcy) levels (28.5 +/- 12.5 vs 16.3 +/- 5.5 micromol/L; P < .05). No differences of tHcy levels have been observed when patients were analyzed according to CyA- or TRL-based immunosuppression regardless of MP or MMF associations. Our data suggest that recipients, particularly those on steroid-based immunosuppression, should receive homocysteine-lowering treatment early after transplantation.     

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.     

Basiliximab and mycophenolate mofetil in combination with low-dose cyclosporine and methylprednisolone effectively prevent acute rejection in kidney transplant recipients

The aim of the study was to analyze whether immunosuppressive treatment with basiliximab and mycophenolate mofetil (MMF), allowed a reduction in methylprednisolone and cyclosporine dosages without increasing the incidence of acute rejection episodes, reducing 1-year graft and patient survivals, or increasing the rates of infections and malignancy in the first year. The two groups were group A (n = 72), treated with methylprednisolone and cyclosporine and in the first 2 weeks with azathioprine; group B (n = 72), treated with basiliximab, MMF, and low-dose cyclosporine and methylprednisolone. The patients were followed for 1 year. The incidence of acute rejection episodes in the first year was significantly lower in group B (2.8%) than group A (12.5%; P < .05). The cumulative methylprednisolone dose, the daily dose, and the average cyclosporine trough blood level were significantly lower in group B (P < .001). One-year serum creatinine was significantly lower in group B (112 +/- 45 micromol/L) than group A (138 +/- 51 micromol/L; P < .01). One-year graft survival was 91.7% in group A and 98.6% in group B. One-year patient survival was 98.6% in group A and 100% in group B. The groups did not differ significantly in the incidence of bacterial, viral, or fungal infections. Immunosuppression with basiliximab and MMF allowed a reduction in cyclosporine and methylprednisolone dosages and was associated with significantly lower incidences of acute rejections episodes with better graft function in the first year as opposed to immunosuppression with higher doses of cyclosporine and methylprednisolone alone. Both immunosuppressive regimens showed the same infection rates and did not differ significantly in the occurrence of malignant diseases within the first year.     

Improvement of renal function in pediatric heart transplant recipients treated with low-dose calcineurin inhibitor and mycophenolate mofetil

BACKGROUND: Renal dysfunction is a major complication in heart transplant recipients treated with calcineurin inhibitors. The goal of the study was to investigate the effect of a reduction of calcineurin inhibitor dosage with the concomitant introduction of mycophenolate mofetil on both renal function and cardiac allograft function. METHODS: Fourteen of 52 consecutive pediatric cardiac allograft recipients experienced a progressive decrease of renal function. A renal biopsy was performed before the dose of calcineurin inhibitors was reduced by 50% and azathioprine was replaced by mycophenolate mofetil. Renal function was evaluated by inulin clearance and maximal urinary osmolality before and yearly after the therapeutic changes. Acute rejection was monitored clinically, by echocardiography and endomyocardial biopsies. RESULTS: Inulin clearance in the fourteen children decreased from 84.2 mL/min/1.73 m at one year posttransplantation to 46.5+/-9.6 mL/min/1.73 m at the time of the change in immunosuppressive therapy. Significant renal lesions were observed in the renal biopsies performed before the change. At 1 year, inulin clearance had increased by 67%. In six patients who had a second determination 2 years after the switch, inulin clearance was not significantly different from the value at 1 year. There were three reversible acute rejection episodes in three patients. The incidence of rejection episodes was not different from a control group of patients whose treatment was not changed. CONCLUSION: The reduction of calcineurin inhibitor dosage and replacement of azathioprine by mycophenolate mofetil is a safe way to improve renal function in children with heart transplants and calcineurin inhibitor induced nephrotoxicity.     

What is the best immunosuppression in living donor liver transplantation?

INTRODUCTION: As we have learned, there are no golden rules of immunosuppression in solid organ transplantation, and every transplant program is using its own regimen to prevent or treat rejection. We have retrospectively analyzed the incidence and severity of acute rejection in a consecutive series of living donor liver transplants. The major objective during the whole study period was to ultimately avoid any steroids from the beginning. METHODS: Twenty one adult patients and five children received 23 right, one left, and two left lateral lobe grafts from genetically or emotionally related living donors, including four ABO-incompatible pairs. The majority of patients had triple initial immunosuppression, based on tacrolimus, mycophenolate mofetil or sirolimus, and basiliximab or daclizumab. Except methylprednisolone administered before reperfusion in 13 patients, only seven had prednisolone after transplantation, and 12/26 had a completely steroid-free regimen. RESULTS: The overall incidence of biopsy-proven acute rejection was 4/21 in adults (19%) and 4/5 in children (80%). Rejections were mild in five and moderate in three cases, respectively, and easily reversed with steroids in all patients. Different combinations of immunosuppressive drugs or ABO incompatibility did not seem to have an influence on the risk of rejection. CONCLUSION: Despite the small number of patients in this series, completely steroid-free triple-drug immunosuppression with tacrolimus, mycophenolate mofetil, and basiliximab is safe and efficient to prevent acute rejection in adult recipients of living donor liver transplants. At least short-term administration of prednisolone should be considered in pediatric patients.     

Triple immunosuppression with or without basiliximab in pediatric renal transplantation: acute rejection rates at one year

Acute rejection (AR) is a major determinant of chronic allograft dysfunction and graft survival. This study evaluated the effect of basiliximab on AR in pediatric renal transplantation on triple immunosuppression. Forty-three transplantations (25 males and 18 females; mean age 14.9 +/- 3.6 years) were performed between 1996 and 2002. Thirteen of the grafts came from cadaveric donors and 30 from living-related donors. All patients were placed on immunosuppression with prednisolone + (azathioprine or mycophenolate mofetil) + (cyclosporine [CYA] or tacrolimus). Basiliximab was also administered in 20 cases. The respective rates of biopsy-proven AR in the basiliximab group (BG) and the standard-regimen group (N-BG) were 0% vs 17.4% (P >.05) at 1 month posttransplantation; 0% vs 26.1% (P <.05) at 3 months; 0% vs 26.1% (P <.05) at 6 months, and 7.1% vs 26.1% (P >.05) at 12 months. In the N-BG group the 1- and 3-year graft survival rates were 91.3% (21/23) and 83.3% (15/18), respectively. The mean glomerular filtration rate (GFR) in the first year after the transplantation was 75 +/- 33 mL/min/1.73 m(2) in the N-BG and 98 +/- 21 mL/min/1.73 m(2) in the BG patients (P <.05).Basiliximab significantly reduced the rates of acute rejection at 3 and 6 months after pediatric renal transplantation. The GFR in the first year was significantly higher among the patients treated with basiliximab, which was well tolerated by all patients and caused no significant adverse effects. The effect of basiliximab on long-term graft survival and chronic allograft dysfunction deserves further investigation.     

Basiliximab (Simulect) in renal transplantation with high risk for delayed graft function

BACKGROUND: Basiliximab (Simulect) is effective in reducing episodes of acute rejection in renal transplantation. Delayed graft function (DGF) predisposes to acute rejection and shortens graft survival. The aim of this study was to determine the effects of basiliximab in renal transplantation recipients at high risk for DGF. METHODS: We studied 87 patients (mean age, 59 years), 42 of whom received basiliximab, 20 mg before transplantation and 20 mg on day 4. This cohort was compared with 45 patients without basiliximab. All received cyclosporine (51%) or tacrolimus (49%), mycophenolate mofetil, and steroids. DGF was defined as the requirement for dialysis within the first week after transplantation or failure to improve preexisting renal function. High-risk factors for DGF were cold ischemia time, recipient and donor age, non-heart-beating donor, HLA matching, and panel reactive antibody (PRA). RESULTS: The incidence of DGF was 18 (43%) in the basiliximab group versus 28 (62%) in the other patients (P = .07). When allografts from non-heart-beating donors were excluded, this incidence was 14 (38%) in the basiliximab group versus 28 (62%) in the other patients (P = .04). Regression analysis showed basiliximab to be a protective factor: 0.26 (range, 0.09-0.76). Basiliximab was well tolerated, and complications were similar in both groups. CONCLUSIONS: Basiliximab reduced the incidence of DGF in patients who received a high-risk allograft. It was well tolerated, and no adverse events were reported. The use of basiliximab may be considered in patients receiving an allograft who are at high risk for DGF.     

Sirolimus and mycophenolate mofetil as calcineurin inhibitor-free immunosuppression in a cardiac transplant patient with chronic renal failure.

Chronic renal failure triggered by calcineurin inhibitor (CNI)-based immunosuppression is a common complication after cardiac transplantation. Sirolimus and mycophenolate mofetil (MMF) are 2 newer immunosuppressive agents with no documented nephrotoxic side effects. This case report describes a patient with ongoing chronic renal failure 10 months after cardiac transplantation on cyclosporine-based immunosuppressive therapy. Conversion of the immunosuppressive regimen from cyclosporine to sirolimus and MMF resulted in freedom from acute rejection, excellent cardiac graft function and consistently improved renal function. This case illustrates the beneficial potential of sirolimus and MMF as CNI-free and safe long-term immunosuppression in a patient with chronic renal failure after heart transplantation.     

Basiliximab-chimeric anti-IL2-R monoclonal antibody in pediatric liver transplantation: comparative study

Basiliximab is a monoclonal antibody that binds to the alpha subunit (CD(25)) of the interleukin-2 receptor of activated T lymphocytes. The advantage of basiliximab in organ transplantation is the reduce possibility to calcineurin inhibitor dosages to avoid nephrotoxicity. Basiliximab has significantly reduced the incidence of acute rejection (AR) in renal transplant recipients; however, the results are uncertain in liver transplantation (LT). The objective of this investigation was to assess the effect of basiliximab to prevent AR in the first 6 months after pediatric LT. From March 2000 to October 2001, 32 recipients of a primary orthotopic cadaveric or living donor LT were given basiliximab by intravenous bolus injection on the day of transplantation (day 0) and on day 4. Four children who received one dose were excluded from the study. The rate and the intensity of AR episodes, the incidence of chronic rejection, serum creatinine level, incidence of infections, adverse side effects, and daily oral dosage of cyclosporine (Neoral) to maintain the target blood level of 850 to 1000 mg/dL at C2, 2 hours after the administration, were analyzed in the remaining 28 recipients. Results were compared to those obtained from a matched historical group (n = 28) of similar age, weight, and hepatic diseases distribution. None of the analyzed parameters was statistically significant (P >.05) except for the daily oral dose of cyclosporine (7 to 13 mg/kg/dose, P <.05). In our series, the addition of basiliximab to the immunosuppressive therapy did not reduce the incidence of AR in pediatric LT.     

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.     

Kidney transplantation in HIV‐positive patients treated with a steroid‐free immunosuppressive regimen

One of the main concerns associated with renal transplantation in HIV‐infected patients is the high risk of acute rejection, which makes physicians reluctant to use steroid‐free immunosuppressive therapy in this subset of patients. However, steroid therapy increases cardiovascular morbidity and mortality. The aim of this study was to define the efficacy of a steroid‐sparing regimen in HIV‐infected renal transplant recipients. Thirteen HIV‐infected patients were consecutively transplanted. The induction therapy consisted of basiliximab and methylprednisolone for 5 days followed by a calcineurin inhibitor plus mycophenolate acid. The mean follow‐up was 50 ± 22 months. Eight patients (61.5%) experienced acute rejection, and 75% of the first episodes occurred within 2 months after transplantation. The probability of first acute rejection was 58% after 1 year and 69% after 4 years. Seven of eight patients recovered or maintained their kidney function after antirejection therapy and steroid resumption. At the last follow‐up, seven of 13 patients (54%) had resumed steroid therapy. The 4‐year patient and graft survivals were 100% and 88.9%, respectively. The benefits of this steroid‐free regimen in HIV‐infected renal recipients must be reconsidered because of the high rate of acute rejection. New immunosuppressive steroid‐free strategies should be identi‐fied in this set of patients.