Living donors: immunologic factors

Transplantations using grafts from living donors were performed on 70 patients with chronic kidney failure, 66 of them involved matching recipients-donors and four involved non-matching recipients-donors. Immunological data were analyzed in 56 pairs of recipients and patients. Of these pairs, one was identical, seven had three identical antigens, 46 were haploidentical at A and B loci, one pair was identical in one antigen and one pair was completely incompatible. The survival of transplanted kidneys largely depended on the degree of histocompatibility. In 33 (59%) transplantations kidneys are functioning from more than 36 months. In the group of seven transplanted pairs with three identical antigens kidneys are functioning in six cases, with four of them functioning from more than 72 months. In the remaining patients (41 patients [73%]) kidneys are functioning, with 8 of them functioning from more than 10 years. The existence of HLA antibodies was investigated. Preimmunization was found in 18 (32%) patients and correlated with the number of blood transfusions. Rejection crises were observed in 12 (21%) patients. As the number of blood transfusions per patient increased the number of rejection crises decreased. Rejection crises were also observed in haploidentical pairs, with a relative risk > 30%. They occurred in the first 2 weeks following transplantation.     

Characteristics of the early postoperative period following kidney allotransplantation and immunosuppression using Sandimmune (cyclosporin A)

The authors analysed the early postoperative period in 100 patients who received sandimmune (cyclosporine A) as the main immunosuppressant after kidney allotransplantation and compared it to that in a control group of 60 patients treated by the usual measures of immunosuppression: azathioprine and steroids. The number of rejection crises was 1.9 times less in the group of patients given sandimmune than in the control group and were more benign in character, while the number of irreversible crises reduced from 26% to 6%. In treatment with sandimmune the dose of oral prednisolone was reduced by 1.9 times and the dose of intravenous methypred by 1.4 times. Nephrotoxicity was the main side effect of sandimmune, it was encountered in 26% of patients. All sandimmune side effects are reversible in decreasing the dose. Sandimmune improves the results of kidney transplantation significantly.     

Mycophenolate mofetil (MMF) versus azathioprine (AZA) in pancreas transplantation: a single-center experience

AIM: Advances in immunosuppression and careful monitoring for rejection are largely responsible for improved results in pancreas transplantation. We conducted a retrospective study to establish the effectiveness of immunosuppressive therapy with mycophenolate mofetil (MMF) instead of azatioprine (AZA) in pancreas transplantation and to assess adverse effects in the two different immunosuppressive regimes. SUBJECTS AND METHODS: Since 1991, 27 pancreas transplantations were performed in 25 patients at our Institute. For induction therapy, immunosuppressant protocol consisted of quadruple immunosuppressive therapy with cyclosporine, steroids, antilymphocyte globulin and AZA in 13 patients or MMF in 12 patients respectively. RESULTS: Acute rejection occurred in 76% of patients in the AZA group compared with 53% in the MMF group. Steroid-resistant rejection was observed in 7% in the MMF group compared to 38% of patients on AZA (p < 0.01). Two kidney grafts were lost due to acute rejection in the AZA group, one pancreas was lost due to acute rejection and one to chronic rejection in the MMF group. There were no significant differences in CMV infection. Severe fungal infections were noted in 2 patients treated with MMF. Malignancy occurred in 1 patient (pancreas graft lymphoma) in MMF. CONCLUSIONS: In conclusion, patients treated with MMF required less frequent and less intensive treatment for acute rejection. However, its short- and long-term side effects should be further investigated.     

Endothelial cell chimerism associated with graft rejection after human lung transplantation

Endotheliitis is a major sign of graft rejection. Recipient-derived endothelial cells found in two series of liver and kidney transplants were related to graft rejection. Here, we assessed the presence and the number of chimeric endothelial cells in lung transplants, and their relation with graft rejection. In six males grafted with female lungs out of 193 lung transplantations, endothelial chimerism was studied by combined XY-fluorescent in situ hybridization with CD31 and CD45 immunostainings and blood group antigens. On samples graded according to the revised working formulation for lung allograft rejection, we found chimeric macrophages (73.1 to 87.2%) in all cases and chimeric endothelial cells (1.3 to 2.1%) in four patients. Another method using ABO blood group also showed endothelial cells positive for recipient-type blood group antigens in three patients. By both methods, presence of chimeric endothelial cells was related to pathological signs of acute rejection (P<0.05).     

The value of platelet transfusions as preparation for kidney transplantation.

The role of platelet transfusion as a preparative method for kidney transplantation is still a matter of debate. Two groups of 28 male patients transplanted between 1983 and 1988, paired for age, date of transplant, absence of anti-HLA antibody and immunosuppressive therapy have been compared. Group I was given 5 purified platelet transfusions at 1-week intervals before transplantation. Each transfusion contained 7.6 x 10(6) platelets contaminated by less than 1 leukocyte in 10(5) platelets. Group II received from 3 to 5 whole blood transfusions. In all cases it was a first transplant from cadaveric donors and previously untransfused patients before entering the protocol. No patient in group I developed cytotoxic antibodies. Acute tubular necrosis occurred with the same incidence in group I and in group II but was more severe and longer in group I, requiring hemodialysis in 62.5% and only 22% in group II. ATN was significantly associated with graft loss in group I (P less than 0.05). The total number of rejections and the number of patients undergoing rejection were not significantly different in both groups. However, the intensity of rejection was significantly higher in group I with 41% (21/51) of severe or irreversible rejections versus 9/46 (19.5%) in group II (P less than 0.05). The first rejection occurred significantly earlier in group I than in group II since 75% of the first rejection episodes occurred in the first 10 days versus 38% in group II (P less than 0.02) with a mean delay of 12.8 +/- 3.2 and 19.10 +/- 3.3 days, respectively. Although platelet transfusions are devoid of leukocytes the incidence of CMV infection was not significantly different in both groups: 57% in group I and 68% in group II. Purified platelet transfusions did not induce humoral immunization but lack of sensitization does not imply indefinite graft prolongation. Because platelets do not carry class II antigens, purified platelets transfusions represent a useful model to analyze the role of class I antigens alone in the induction of unresponsiveness in organ transplantation.     

肝移植术后患者应用免疫抑制剂的单中心经验总结(附1400例分析)

目的总结对肝移植术后患者应用免疫抑制剂的经验,探讨个体化治疗的可行性。方法回顾分析2002年4月至2010年8月单中心1400例肝移植患者的临床资料。术后免疫抑制治疗方案的制定按时间发展经历了3个阶段:(1)第1阶段(2002年4月至2004年12月)311例患者采用传统免疫抑制治疗方案;(2)第2阶段(2005年1月至2007年12月)618例患者采用部分传统免疫抑制剂减量的方案;(3)第3阶段(2008年1月至2010年8月)471例患者采用个体化免疫抑制治疗方案。再按术前终末期肝病模型(modelforend-stageliverdisease,MELD)评分及肿瘤是否超出米兰标准分为常规组、超米兰标准组和重症组。收集3个阶段肝移植患者的生存情况,绘制生存曲线。观察第3阶段3组患者的排斥反应发生情况,了解免疫抑制剂其他不良反应及药物替换情况。结果第1、第2、第3阶段患者生存率呈逐渐升高趋势。第3阶段采用个体化治疗,3组的免疫抑制剂用量不同,但3组间免疫排斥反应发生率差异无统计学意义(均为P>0.05)。第3阶段共将12例患者的他克莫司(FK506)转换为环孢素(CsA),32例患者因肾功能损害将FK506转换为小剂量FK506+麦考酚吗乙酯(MMF)或西罗莫司,病情得以缓解。因肿瘤因素或肾功能异常应用单独应用西罗莫司27例,3例因为高脂血症或口腔溃疡不能耐受西罗莫司。结论肝移植术后免疫抑制剂的个体化治疗是可行的,可减少免疫抑制剂的用量,又不增加排斥反应发生率,有利于提高患者生存率。     

乙型肝炎相关性肝病肝移植术后的急性排斥反应

目的 研究乙型肝炎相关性肝病肝移植术后急性排斥反应的发病率、治疗和预防。方法前瞻性地研究用肝移植术治疗乙型肝炎相关性肝病100例，分析急性排斥反应的发病相关因素，急性排斥反应和免疫抑制剂治疗的动态监测及二者间的联系。结果临床型急性排斥反应的发病率为12％，急性排斥反应发生前3～5d，有明显的免疫抑制剂浓度降低的过程。FKS06为基础的免疫抑制方案，加用骁悉，可有效地终止、逆转急性排斥反应；和以甲基强的松龙冲击治疗急性排斥反应相比较，副作用少，但肝功能的完全恢复时间相对较慢。结论乙型肝炎相关性肝病的肝移植术后急性排斥反应的发生率相对较低；和急性排斥反应发生相关的免疫抑制剂低浓度是诱导急性排斥反应的重要相关因素；FK506为基础的免疫抑制方案，可有效地终止、逆转急性排斥反应，且副作用少。     

Cell-mediated immunity to donor antigens in renal allograft recipients.

The antigen-stimulated active rosette-forming T-cell (AgARFC) assay was adapted for the preoperative study of 21 consecutive kidney transplants (17 cadaver donors and four living related donors; five retransplants). Recipient peripheral blood lymphocytes were incubated for 15 minutes with donor histocompatibility antigens preparaed by sonication of donor peripheral blood or splenic lymphocytes. Recipient presensitization to donor antigens was expressed as the difference between active rosette formation in the presence (%AgARFC) and in the absence (%ARFC) of donor antigens. This antigen-induced difference is rosette formation (%AgARFC - %ARFC) for all patients ranged from - 7.0% to 24.2%. Of those patients with pretransplant sensitization greater than 6.3% (group I: mean, 13.2 +/- 3.0; n = 7), 71% had severe acute rejection requiring dialysis within the first 2 weeks of transplantation. In contrast, none of the patients with pretransplant values below 6.3% (group II: mean, -0.8 +/- 1.0; n = 14) had rejection requiring dialysis within the first 2 weeks. Group I patients had 43% graft survival at 1 month and 14% survival at 2 months, whereas group II had 86% graft survival at 1 month and 71% at 2 months. The AgARFC assay provided a rapid means of measuring recipient T-cell presensitization to donor alloantigens, which was correlated with the accelerated rejection of renal allografts.     

Tacrolimus rescue in liver transplant patients with refractory rejection or intolerance or malabsorption of cyclosporine. The US Multicenter FK506 Liver Study Group.

Tacrolimus is an effective immunosuppressant in the rescue of liver allograft patients in whom conventional immunosuppression failed. Efficacy and safety were examined in a multicenter trial of liver transplant recipients converted to tacrolimus because of rejection despite cyclosporine (CyA) therapy or intolerance to CyA. Six hundred seventy-seven patients were enrolled onto the study; 475 patients for rejection, 197 patients for intolerance, and 5 patients treated compassionately. The mean daily dose of tacrolimus was less in the intolerance (Int) patients throughout the study: 0.22 versus 0.17 mg/kg at 1 week and 0.14 versus 0.11 mg/kg at 24 months in rejection (Rej) and Int patients, respectively. Mean blood levels paralleled dosing in both groups, but were greater in the Rej patients (10.7 v 8.3 ng/mL at 18 months). Kaplan-Meier estimates of patient and graft survival were similar in the two groups. Patient survival rates were 80.1% and 81.5%, and graft survival rates were 72.7% and 73.9% at 24 months in the Rej and Int patients, respectively. Most adverse events occurred with a similar incidence in the two groups. Those with a 4% or greater incidence were fever, viral hepatitis, and pneumonia. The incidence of sepsis, gastrointestinal hemorrhage, kidney failure, and convulsion was greater in the Int group. The incidence of abnormal liver function test results, hyperglycemia, headache, and abnormal kidney function was greater in the Rej group. Mean liver function test results decreased with time postrescue in both groups. Mean serum creatinine level increased from baseline to 18 months postrescue in both groups (1.44 to 1.51 mg/dL for Int patients, 1.14 to 1.48 mg/dL for Rej patients). We conclude tacrolimus is safe and effective rescue in liver transplant recipients with rejection or CyA intolerance.     

Comparison between a two-drug regimen with tacrolimus and steroids and a triple one with azathioprine in kidney transplantation: results of a European trial with 3-year follow up

This study was designed to assess the efficacy and safety of two immunosuppressant regimens in kidney transplantation based on the administration of tacrolimus-one of them with tacrolimus, azathioprine, and corticosteroids (n=239) and the other with tacrolimus, and corticosteroids (n=236). After completing the initial 3-month study, the patients remaining in the study (197 and 195, respectively) were assessed for 3 years. The incidence of acute rejection (AR) episodes treated during this period was 28.8% with dual-drug therapy and 29.7% with triple-drug therapy. Late AR: episodes between 4 and 36 months were scarce (3.3% in dual and 4.2% in triple therapy). Chronic rejection incidence was 7.7% and 8.9%, respectively. The patients who experienced AR episodes during the first 3 months developed chronic rejection more frequently than those who did not suffer AR. Patient survival at 3 years was 95% vs 95.6%, and graft survival was 86.6% vs 86.5% (NS). Doses and blood levels of tacrolimus were similar in the two groups. Adverse effects were similar among both treatment groups. Median SCr was 123.8 micromol/L vs 114.9 micromol/L in patients who did experience AR: 145.9 micromol/L vs 132.6 micromol/L in those with early AR; and 194.5 micromol/L vs 152 micromol/L in those who presented with late AR. Need for de novo posttransplant insulin was 4.2% in the dual-drug group and 3.8% in the triple-drug cohort. These results demonstrate that, after 3 years of follow up, there were similar efficacy data among the dual- and triple-drug regimens. Thus, addition of azathioprine does not contribute any advantage in the middle term.     

Clinical Significance of an Early Protocol Biopsy in Living-Donor Renal Transplantation: Ten-Year Experience at a Single Center

We report here our 10-year experience of a biopsy performed at day 14 after transplantation in 304 patients with stable graft function. The factors that may have influenced subclinical rejection were analyzed according to histology. The incidence of subclinical rejection was 13.2%. Addition of mycophenolate mofetile (MMF) as a primary immunosuppressant significantly decreased the incidence of subclinical rejection compared with patients without such treatment (odds ratio, 0.23; p < 0.05). On the other hand, HLA-DR antigen mismatch (odds ratio, 2.39) and unrelated donor (odds ratio, 2.10) were also significantly associated with decreased subclinical rejection (p < 0.05). The incidence of acute rejection in patients with normal findings was lower than in those with borderline changes or subclinical rejection (0.23 +/- 0.05 vs. 0.48 +/- 0.07 and 0.60 +/- 0.11, respectively; p < 0.05). The graft survival rates in patients with subclinical rejection were lower than in patients with normal or borderline changes at 1 (88.4% vs. 97.9% and 99.1%; p < 0.05), 5 (77.8% vs. 96.2% and 95.9%; p < 0.05) and 10 (62.3% vs. 96.2% and 93.7%; p < 0.05) years. Thus, a protocol biopsy performed on day 14 after transplantation is useful for predicting graft survival. Triple therapy including MMF, related donor and HLA-DR antigen match are important factors for reducing subclinical rejection in living-donor renal transplantation.     

Renal cadaveric transplantation in diabetics using total lymphoid irradiation or cyclosporin A: A controlled randomized study

Abstract. A total of 20 renal transplant patients with end-stage diabetic nephropathy entered a randomized controlled trial comparing preoperative, fractionated total lymphoid irradiation (TLI) (radiation dose, 20–30 Gy) with postoperative cyclosporin A (CsA). Both groups received postoperative low-dose methylprednisolone maintenance therapy. The 3-year patient and graft survival was similar for both groups (100% and 71% in the TLI and 75% and 75% in the CsA group, respectively). Rejection crises occurred significantly more frequently ( P < 0.01) in the TLI-treated recipients. The incidence of infectious or diabetic complications was not significantly different in both groups. It is concluded that TLI and CsA are both effective treatment modalities for cadaveric renal transplantation in diabetics; CsA, however, is superior in preventing rejection crises.     

Results of orthotopic heart transplantation with and without the use of maintenance steroids

From March 1984 to June 1987, 51 patients underwent primary orthotopic heart transplantation at the Second University Department of Surgery, Vienna. Recipients were immunosuppressed with a combination of either ciclosporine and azathioprin (double drug regimen = DD, 10 patients), or ciclosporine, azathioprin and low-dose steroids (triple drug regimen = TD, 33 patients). Four patients who died intra- or perioperatively and 4 who were switched to conventional therapy were excluded from analysis. In both groups, ciclosporine was administered to obtain whole blood HPLC trough levels of 200-400 ng/ml in the 1st month, 150-250 ng/ml from the 2nd to the 6th and 100-150 ng/ml after the 6th month. Azathioprin 2 mg/kg per day was given, and in TD patients, an additional 0.2 mg/kg per day of prednisolon: all patients received prophylactic antithymocyte globulin for 7-10 days postoperatively. Five deaths from acute rejection in the DD group contrasted with none in the TD group. The high incidence of fatal rejection episodes was reflected in a 40% Kaplan-Meier 1-year survival for DD vs 84% for TD (p less than 0.0001). Analysis of endomyocardial biopsies (DD vs TD) demonstrated 20.4% vs 57.0% absent, 46.0% vs 29.5% mild, 31.2% vs 12.4% moderate and 2.4% vs 1.1% severe rejection. Fatal and nonfatal infections and toxic side effects occurred with the same frequency in both protocols. Calculation of mean ciclosporine levels resulted in 249.7 ng/ml (TD) and 206.0 ng/ml (DD) in the 1st month (p less than 0.05). Consequently, adjunctive maintenance low-dose steroids combined with increased ciclosporine levels in the early posttransplant course are considered responsible for the improved results.     

Diabetes mellitus after renal transplantation in the cyclosporine era--an analysis of risk factors

Despite mounting experimental evidence that cyclosporine inhibits pancreatic islet cell function, clinical data on posttransplant diabetes mellitus (PTDM) in renal allograft recipients in the cyclosporine era are scarce. Between June 1983 and December 1988, 39 of 337 (11.6%) cyclosporine-treated adult renal transplant recipient whose grafts survived longer than 1 year developed PTDM. Of these, 43.6% and 74.4% were diagnosed by 3 and 12 months posttransplant, respectively, and 51.3% were insulin-dependent. Incidence of PTDM was highest in blacks (19.8%) and Hispanics (21.3%) and in those with HLA-A 30 and Bw 42 antigens. Older recipients and those that received cadaveric kidneys were more likely to develop diabetes than those who received living related allografts (14% vs. 5.3%, P less than 0.05). The rate of PTDM appeared to be independent of the type of induction, immunosuppressant therapy, incidence of rejection, total steroid and cyclosporine dose, percentage of body weight gain in the first posttransplant year, and serum creatinine concentration. Actuarial 5-year, decaying from 100% at 1 year, patient and graft survival rates were 87% and 70%, respectively, in the PTDM group compared with 93% and 90%, respectively, in controls. Causes of graft failure among the diabetics included chronic rejection (6), patient death (3), noncompliance with immunosuppressants (2), and sepsis (1). The incidence of infectious complications was significantly higher in the PTDM group compared with the control group (53% vs. 16%, P less than 0.05), with all 5 deaths among the diabetics being sepsis-related.     

供者DC介导的淋巴细胞反应在肾移植后个体化免疫抑制治疗中的作用

目的 探讨根据供者骨髓源性树突状细胞(DC)介导肾移植受者淋巴细胞反应指导肾移植术后免疫抑制剂个体化应用的价值。方法 2008年1月至2010年1月间接受亲属活体供肾移植者30例,根据药物剂量调整依据的不同分为试验组和对照组,每组各15例,免疫抑制方案同为他克莫司(Tac)+吗替麦考酚酯(MMF)+皮质激素。试验组术后根据受者淋巴细胞对供者DC的反应强度,结合血Tac、MMF浓度调整药物剂量;对照组术后仅根据血药浓度调整药物剂量。术后每月检查肝功能、肾功能、血常规、尿常规、血糖,随访时间为1年。结果 随访期内试验组急性排斥反应的发生率为13.3％,对照组为46.7％(P＜0.05);试验组和对照组的感染发生率分别为6.7％和40.0％(P＜0.05);试验组和对照组不良反应的总体发生率分别为13.3％和46.7％(P＜0.05)。两组各时间点的血清肌酐的差异无统计学意义(P＞0.05)。结论 利用供者骨髓源性DC介导肾移植受者淋巴细胞反应结合治疗药物血药浓度监测作为免疫监测指标,指导肾移植术后免疫抑制剂个体化应用,较仅利用血药浓度监测更全面、准确。     

Outcome of cardiac transplant recipients with a positive donor-specific crossmatch--preliminary results with plasmapheresis.

To assess the influence of a positive T or B cell IgG crossmatch on the development of rejection and mortality following cardiac transplantation, we reviewed all cardiac transplants performed in Utah between March 1985 and October 1990. Of the 328 cardiac allograft recipients, 11 (3.4%) had an IgG positive crossmatch. Actuarial survival at 24 months in the positive crossmatch group was 57.3% +/- 0.02 while that of the controls was 86.1% +/- 2.1 (P < 0.05). Allograft rejection occurred earlier in recipients with a positive crossmatch (10.0 +/- 5.8 days versus 34.0 +/- 2.3 days, P < 0.001). The first allograft rejection episode in patients with a positive crossmatch was characterized by immunoglobulin and complement deposition in small blood vessels and interstitial edema and endothelial cell activation in the absence of a lymphocytic infiltrate. Furthermore, the allograft rejection in the positive crossmatch group was accompanied by hemodynamic compromise in a large proportion of the patients (73%). In addition to augmentation of immunosuppression, plasma exchange therapy was performed within the first week following transplantation in 8 of the 11 positive crossmatch patients. Survival in the patients treated with plasma exchange (75%) appears to be better than in those not receiving plasma exchange (33%) within one week of transplantation. While immunosuppressive therapy aimed at the humoral arm of the immune system and plasma exchange therapy may improve survival in recipients with a positive donor-specific crossmatch, survival is worse in patients with a positive crossmatch than in patients with a negative crossmatch. Thus, it would appear prudent to prospectively crossmatch cardiac transplant candidates with a greater risk of developing a positive crossmatch, such as those potential recipients with an elevated level of panel-reactive antibodies.     

Renal cadaveric transplantation in diabetics using total lymphoid irradiation or cyclosporin A

A total of 20 renal transplant patients with end-stage diabetic nephropathy entered a randomized controlled trial comparing preoperative, fractionated total lymphoid irradiation (TLI) (radiation dose, 20–30 Gy) with postoperative cyclosporin A (CsA). Both groups received postoperative low-dose methylprednisolone maintenance therapy. The 3-year patient and graft survival was similar for both groups (100% and 71% in the TLI and 75% and 75% in the CsA group, respectively). Rejection crises occurred significantly more frequently (P<0.01) in the TLI-treated recipients. The incidence of infectious or diabetic complications was not significantly different in both groups. It is concluded that TLI and CsA are both effective treatment modalities for cadaveric renal transplantation in diabetics; CsA, however, is superior in preventing rejection crises.     

Is serial iodohippurate renography at the bedside reliable enough to monitor renal transplants?

Renograms were obtained immediately after transplantation and repeated every other day beginning 4 days after renal transplantation. In 31 of 32 biopsy-proved acute rejection crises a flattening of phase II (secretion phase) of the renogram occurred. Of the 32 renogram changes 7 were the only signs of rejection at the time of renography. This finding confirms our previous impression based on 116 rejection episodes (diagnosed according to clinical symptoms and response to therapy) that phase II alteration in serial renograms is a sensitive and probably specific sign of rejection. Because this simple method to monitor renal transplantation is not invasive, can be done at the bedside, and gives immediate and easily interpreted results repeated renography is recommended as the basic screening method. Renography is helpful especially in patients with acute tubular necrosis after renal transplantation. The need for more invasive diagnostic procedures, such as renal biopsy and angiography, can be shown by such renograms, although this has occurred rarely in our experience.     

Impact of Rh(D) blood group system on graft function and survival in live-donor kidney transplantation: a single-institution experience

One thousand five hundred consecutive live-donor renal transplants were performed in a single institution. Among these patients, 1,372 patients (group I) received Rh-identical allografts and 128 (group II) received Rh-nonidentical allografts. The two groups were homogenous apart from the prevalence of the Rh nonidentity among unrelated donor-recipient pairs. The rate of acute and chronic rejection was comparable in both groups (P = 0.33 for acute rejection and P = 0.66 for chronic rejection). The mean serum creatinine at 5 years was 1.8 +/- 1 mg/dL for group I and 1.7 +/- 0.9 mg/dL for group II (P = 0.5). The 1-, 5-, and 10-year graft survival rates were 94%, 78%, and 54% for group I and 95%, 82%, and 57% for group II. We found that the Rh(D) blood group system is not likely to be a clinically relevant histocompatibility barrier to live-donor renal transplantation.     

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.