Indications:Kidney graft rejection prophylaxis in 62 patients who underwent kidney transplantation. Concomitant diseases: Addison disease (1), systemic lupus erythematosus (1).; Patients:62 patients (37 males, 25 females; mean age, 42 ± 11.2 years; range, 22 to 68 years). 57 received grafts from living-related donors, 5 from cadaveric kidneys. Follow-up period was 3 months. Control steroid maintained (non-Simulect) group: 56 patients, 27 male, 29 female, mean age 39.0 years.; DosageDuration:20 mg, as 2 bolus iv doses on days 0 and 4. Single drug doses.; TypeofStudy:Clinical outcome of early steroid withdrawal protocol using Simulect in kidney transplantation was investigated. Comparative clinical study in which early steroid withdrawal patients received Simulect combined with cyclosporin A or tacrolimus, mycophenolate mofetil and short-course methylprednisolone for rejection prophylaxis, with outcomes being compared with those in a control steroid-maintained group treated with steroid, cyclosporin A or tacrolimus, mycophenolate mofetil or azathioprine, antilymphocyte globulin and muromonab.; Results:Five cases were excluded from those undergoing a rapid steroid withdrawal protocol. In these cases a low dose of steroid was continued. Among the remaining 57 cases, steroid was discontinued at 13.7 ± 1.7 postoperative days. In 11 cases steroid was resumed at 20 to 114 days after transplantation. Thus in 46 cases of 62 (74.2%), steroid was completely withdrawn. No difference in AUC0-4 and C2 level of CsA was evident between ABO-compatible and ABO incompatible cases in any postoperative week. As for the mean dose of MMF, no difference was noted between ABO-compatible and ABO incompatible cases and between cadaveric and living-related cases at any time. The period of recovery of CD25 incidence to the previous value was 7 weeks in the earliest case and more than 17 weeks in the latest case. One-, 3- and 6-month cumulative patient and graft survival rates were 100%. The average sCr was 1.80± 1.43 mg/dL at 1 month, 1.47 ± 0.72 mg/dL at 3 months, and 1.33 ± 0.43 mg/dL at 6 months. Biopsy-proven acute rejection occurred as 8 episodes (12.9%) in 7 patients (11.3%). Complete remissions were achieved in all cases: 4 cases were treated with only steroid pulse therapy, and three cases diagnosed as humoral rejection were treated with steroid pulses in combination with DFPP or deoxyspergualin. Positive CMV antigenemia was observed in 15 cases (24.2%) at 4 to 47 days after the transplantation. Symptomatic CMV-related infectious disease was observed in 3 cases (4.8%). Posttransplant complications included urinary leakage in 3 cases, lymphocele in 2 cases, minimal intraabdominal hematoma after splenectomy in 2 cases, hydronephrosis in 2 cases, and intravertebral discitis in 1 case. These subjects were compared with another group treated with the regimen consisting of CNI, MMF, and steroids, in which ALG with or without DSG induction was added incases of ABO-incompatibility. The incidence of rejection episodes in group A, namely 8 (12.9%) in 7 patients (11.3%) was significantly lower than that in group B namely 28 (50%) in 24 patients (42.9%). Six rejection episodes of 28 in group B required muromonab CD3 therapy but none of 8 episodes in group A. The incidence of CMV antigenemia was almost equal between the two groups (24.2% vs 23.2%), whereas the incidence of CMV-related febrile episodes in group A was lower than that in group B (4.8% vs 8.9%). Eight episodes of CMV antigenemia of 13, and all 5 episodes of CMV disease in group B occurred after a rejection episode, with 3 of 5 episodes of CMV observed among patients treated with muromonab CD3, while 4 episodes of CMV antigenemia of 15 and 2 episodes of CMV disease of three in group A evolved after a rejection episode in CMV IgG-negative cases.; AdverseEffects:3 patients had cytomegalovirus infection and 15 had cytomegalovirus antigenemia.; AuthorsConclusions:Steroids were successfully discontinued early after kidney transplantation by using basiliximab in combination with CNI and MMF. Cumulative patient and graft survival rates were 100% at 3 and 6 months, and eight rejection episodes (12.9%) occurred in seven patients (11.3%) among 62 recipients. All rejection episodes were successfully treated with steroid pulses without ALG or muromonab CD3. The incidence of CMV antigenemia and CMV-related febrile episodes without any organ involvement was 24.2% and 4.8%, respectively. Neither posttransplant diabetes (PTDM) nor any other steroid related adverse effects including cataract, ocular hypertension, aseptic necrosis, or peptic ulcer were observed during the observation period.; FreeText:Among 64 patients who underwent kidney transplantation, 62 enrolled in an early steroid withdrawal protocol and were followed for more than 3 months. Recipient splenectomy was done in all cases of ABO-incompatible kidney transplantation during the transplant operation except for four cases in which the titer of anti-A or anti-B antibody remained over 1:16 despite double filtration plasmapheresis (DFPP). Immunosuppressant regimen consisted of methylprednisolone (MPL) which was rapidly tapered and withdrawn at 14 posttransplant days, Simulect, 8 mg/kg of cyclosporin A (CsA), (n= 61 cases) or 0.1 mg/kg of tacrolimus (Tac, n=1), and 2000 mg daily of mycophenolate mofetil (MMF). Both CsA and MMF were given perorally beginning 2 days before transplantation, followed by IV administration of 3 mg/kg of CsA for 24 hours after the transplantation. Thereafter the dosage of CsA was adjusted. In case of a clinically diagnosed or biopsy-proven acute rejection episode, steroid pulse therapy was administered (twice intravenous administration of 500 mg of MPL thereafter quickly tapered). In case of humoral rejection confirmed by graft biopsy with or without positive anti-donor or anti-HLA antibody determined by complement-dependent cytotoxicity or flow cytometry lymphocyte crossmatch or panel reactive antibody, DFPP was done to eliminate the antibody. The serum level of creatinine (sCr) was determined daily to assess graft function, and Doppler ultrasonography was done to examine the blood flow velocity and calculate the resistive index. The incidence of rejection episodes, cumulative patient and graft survival rates and incidence of cytomegalovirus (CMV) antigenemia and disease in patients treated with the early steroid withdrawal regimen were compared to those who underwent kidney transplantation with a regimen of calcineurin inhibitor (CNI), antimetabolite, and steroid, in which antilymphocyte globulin (ALG) with or without deoxyspergualin was added at induction in cases of ABO-incompatible cases.; Indications:Kidney graft rejection prophylaxis in 108 patients who underwent kidney transplantation. Concomitant diseases: Addison disease (1), systemic lupus erythematosus (1).; Patients:62 patients (37 males, 25 females; mean age, 42 ± 11.2 years; range, 22 to 68 years). 57 received grafts from living-related donors, 5 from cadaveric kidneys. Sandimmun n=61, Tacrolimus n=1. Follow-up period was 3 months. Control steroid maintained (non-basiliximab) group: 56 patients, 27 male, 29 female, mean age 39.0 years. Sandimmun group: 47 patients. Tacrolimus group: 9 patients.; TypeofStudy:Clinical outcome of early steroid withdrawal protocol using basiliximab in kidney transplant recipients under Sandimmun-based immunosuppression was investigated. Comparative clinical study in which early steroid withdrawal patients received basiliximab combined with Sandimmun or tacrolimus, mycophenolate mofetil and short-course methylprednisolone for rejection prophylaxis, with outcomes being compared with those in a control steroid-maintained group treated with steroid, Sandimmun or tacrolimus, mycophenolate mofetil or azathioprine, antilymphocyte globulin, deoxyspergualin and muromonab.; DosageDuration:Initially 8 mg-kg daily orally for 2 days, then 3 mg-kg daily iv for 24 hours, then oral dose adjusted according to blood levels. Duration: 1 year.; Results:Five cases were excluded from those undergoing a rapid steroid withdrawal protocol. In these cases a low dose of steroid was continued. Among the remaining 57 cases, steroid was discontinued at 13.7 ± 1.7 postoperative days. In 11 cases steroid was resumed at 20 to 114 days after transplantation. Thus in 46 cases of 62 (74.2%), steroid was completely withdrawn. No difference in AUC0-4 and C2 level of Sandimmun was evident between ABO-compatible and ABO incompatible cases in any postoperative week. As for the mean dose of MMF, no difference was noted between ABO-compatible and ABO incompatible cases and between cadaveric and living-related cases at any time. The period of recovery of CD25 incidence to the previous value was 7 weeks in the earliest case and more than 17 weeks in the latest case. One-, 3- and 6-month cumulative patient and graft survival rates were 100%. The average sCr was 1.80± 1.43 mg/dL at 1 month, 1.47 ± 0.72 mg/dL at 3 months, and 1.33 ± 0.43 mg/dL at 6 months. Biopsy-proven acute rejection occurred as 8 episodes (12.9%) in 7 patients (11.3%). Complete remissions were achieved in all cases: 4 cases were treated with only steroid pulse therapy, and three cases diagnosed as humoral rejection were treated with steroid pulses in combination with DFPP or deoxyspergualin. Positive CMV antigenemia was observed in 15 cases (24.2%) at 4 to 47 days after the transplantation. Symptomatic CMV-related infectious disease was observed in 3 cases (4.8%). Posttransplant complications included urinary leakage in 3 cases, lymphocele in 2 cases, minimal intraabdominal hematoma after splenectomy in 2 cases, hydronephrosis in 2 cases, and intravertebral discitis in 1 case. These subjects were compared with another group treated with the regimen consisting of CNI, MMF, and steroids, in which ALG with or without DSG induction was added incases of ABO-incompatibility. The incidence of rejection episodes in group A, namely 8 (12.9%) in 7 patients (11.3%) was significantly lower than that in group B namely 28 (50%) in 24 patients (42.9%). Six rejection episodes of 28 in group B required muromonab CD3 therapy but none of 8 episodes in group A. The incidence of CMV antigenemia was almost equal between the two groups (24.2% vs 23.2%), whereas the incidence of CMV-related febrile episodes in group A was lower than that in group B (4.8% vs 8.9%). Eight episodes of CMV antigenemia of 13, and all 5 episodes of CMV disease in group B occurred after a rejection episode, with 3 of 5 episodes of CMV observed among patients treated with muromonab CD3, while 4 episodes of CMV antigenemia of 15 and 2 episodes of CMV disease of three in group A evolved after a rejection episode in CMV IgG-negative cases.; AdverseEffects:1 patient had nephrotoxicity, and unspecified numbers had cytomegalovirus infection or antigenemia.; AuthorsConclusions:Steroids were successfully discontinued early after kidney transplantation by using basiliximab in combination with calcineurin inhibitor and MMF.; FreeText:Among 64 patients who underwent kidney transplantation, 62 enrolled in an early steroid withdrawal protocol and were followed for more than 3 months. Recipient splenectomy was done in all cases of ABO-incompatible kidney transplantation during the transplant operation except for four cases in which the titer of anti-A or anti-B antibody remained over 1:16 despite double filtration plasmapheresis (DFPP). Immunosuppressant regimen consisted of methylprednisolone (MPL) which was rapidly tapered and withdrawn at 14 posttransplant days, two bolus IV injections of 20 mg basiliximab, Sandimmun or 0.1 mg/kg of tacrolimus (Tac, n=1), and 2000 mg daily of mycophenolate mofetil (MMF). Both Sandimmun and MMF were given perorally beginning 2 days before transplantation, followed by IV administration of 3 mg/kg of Sandimmun for 24 hours after the transplantation. Thereafter the dosage of Sandimmun was adjusted. In case of a clinically diagnosed or biopsy-proven acute rejection episode, steroid pulse therapy was administered (twice IV administration of 500 mg of MPL thereafter quickly tapered). In case of humoral rejection confirmed by graft biopsy with or without positive anti-donor or anti-HLA antibody determined by complement-dependent cytotoxicity or flow cytometry lymphocyte crossmatch or panel reactive antibody, DFPP was done to eliminate the antibody. The serum level of creatinine (sCr) was determined daily to assess graft function, and Doppler ultrasonography was done to examine the blood flow velocity and calculate the resistive index. The incidence of rejection episodes, cumulative patient and graft survival rates and incidence of cytomegalovirus (CMV) antigenemia and disease in patients treated with the early steroid withdrawal regimen were compared to those who underwent kidney transplantation with a regimen of calcineurin inhibitor (CNI), antimetabolite, and steroid, in which antilymphocyte globulin (ALG) with or without deoxyspergualin was added at induction in cases of ABO-incompatible cases.
