Shapiro Ron, Ellis Demetrius, Tan Henkie P, Moritz Michael L, Basu Amit, Vats Abhay N, Khan Akhtar S, Gray Edward A, Zeevi Adrianna, McFeaters Corde, James Gerri, Jo Grosso Mary, Marcos Amadeo, Starzl Thomas E
Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA.
J Pediatr. 2006 Jun;148(6):813-8. doi: 10.1016/j.jpeds.2006.01.008.
Heavy post-transplant immunosuppression may contribute to long-term immunosuppression dependence by subverting tolerogenic mechanisms; thus, we sought to determine if this undesirable consequence could be mitigated by pretransplant lymphoid depletion and minimalistic post-transplant monotherapy.
Lymphoid depletion in 17 unselected pediatric recipients of live (n = 14) or deceased donor kidneys (n = 3) was accomplished with antithymocyte globulin (ATG) (n = 8) or alemtuzumab (n = 9). Tacrolimus was begun post-transplantation with subsequent lengthening of intervals between doses (spaced weaning). Maintenance immunosuppression, morbidity, graft function, and patient/graft survival were collated.
Steroids were added temporarily to treat rejection in two patients (both ATG subgroup) or to treat hemolytic anemia in two others. After 16 to 31 months (mean 22), patient and graft survival was 100% and 94%, respectively. The only graft loss was in a nonweaned noncompliant recipient. In the other 16, serum creatinine was 0.85 +/- 0.35 mg/dL and creatinine clearance was 90.8 +/- 22.1 mL/1.73 m2. All 16 patients are on monotherapy (15 tacrolimus, one sirolimus), and 14 receive every other day or 3 times per week doses. There were no wound or other infections. Two patients developed insulin-dependent diabetes.
The strategy of lymphoid depletion and minimum post-transplant immunosuppression appears safe and effective for pediatric kidney recipients.
移植后强效免疫抑制可能通过破坏致耐受性机制导致长期免疫抑制依赖;因此,我们试图确定这种不良后果是否可通过移植前淋巴细胞清除和简化的移植后单一疗法来减轻。
17名未选择的小儿活体供肾(n = 14)或尸体供肾(n = 3)受者接受淋巴细胞清除,使用抗胸腺细胞球蛋白(ATG)(n = 8)或阿仑单抗(n = 9)。移植后开始使用他克莫司,随后延长给药间隔(间隔撤药)。整理维持性免疫抑制、发病率、移植肾功能以及患者/移植肾存活率。
两名患者(均为ATG亚组)临时加用类固醇以治疗排斥反应,另外两名患者加用类固醇以治疗溶血性贫血。16至31个月(平均22个月)后,患者和移植肾存活率分别为100%和94%。唯一的移植肾丢失发生在一名未撤药且不依从的受者。在其他16名患者中,血清肌酐为0.85±0.35 mg/dL,肌酐清除率为90.8±22.1 mL/1.73 m²。所有16名患者均接受单一疗法(15名使用他克莫司,1名使用西罗莫司),14名患者每隔一天或每周3次给药。未发生伤口或其他感染。两名患者发展为胰岛素依赖型糖尿病。
淋巴细胞清除和最小化移植后免疫抑制策略对小儿肾移植受者似乎安全有效。