Alloway R R, Hanaway M J, Trofe J, Boardman R, Rogers C C, Hanaway M J, Buell J F, Munda R, Alexander J W, Thomas M J, Roy-Chaudhury P, Cardi M, Woodle E S
Division of Transplantation, University of Cincinnati, Cincinnati, Ohio 45249, USA.
Transplant Proc. 2005 Mar;37(2):802-3. doi: 10.1016/j.transproceed.2004.12.129.
The first prospective trial of steroid withdrawal dedicated to high-immunologic-risk patients is reported herein.
Twenty-five patients were enrolled prospectively in an IRB-approved HIPAA-compliant protocol. Immunosuppression included corticosteroid withdrawal (CSWD) at 7 days, tacrolimus (target trough level 4 to 8 ng/mL), sirolimus (target trough level 8 to 12 ng/mL), and Mycophenolate Mofetil (2 g/d). Induction with daclizumab (2 mg/kg) on posttransplant days (PTD) 0 and 14 was administered to the first 10 patients. The protocol for the next 15 patients was modified because of high acute rejection rates to include received T-cell-depleting antibody induction therapy with thymoglobulin (1.5 mg/kg) on PTDs 0 and 2 followed by daclizumab on Postoperative day (POD) 14. Recipient inclusion criteria included: (1) repeat transplant recipients; or (2) patients with a peak PRA > or =25%. All rejection episodes were diagnosed by biopsy and graded using Banff '97 criteria.
Twenty-five patients were enrolled and median follow-up was 402 days. Forty percent of recipients were black, 68% of patients were repeat transplant recipients, 68% received deceased donor kidneys, and 36% had a peak flow PRA >25%. Overall acute rejection, graft survival, and patient survival rates of 40%, 88%, and 96%, respectively, were observed for the duration of the study. Acute rejection occurred in 6 of 10 patients (60%) with daclizumab induction; however, acute rejection rates fell to 27% when thymoglobulin was introduced (P = .1).
This study supports our previous observations in a multivariate analysis of early CSWD patients, wherein polyclonal antibody induction therapy reduced acute rejection. High-immunologic-risk patients may be able to undergo early CSWD with acceptable rates of acute rejection.
本文报告了首个针对高免疫风险患者的类固醇撤减前瞻性试验。
25例患者前瞻性纳入一项经机构审查委员会（IRB）批准且符合《健康保险流通与责任法案》（HIPAA）的方案。免疫抑制包括在第7天进行皮质类固醇撤减（CSWD）、他克莫司（目标谷浓度4至8 ng/mL）、西罗莫司（目标谷浓度8至12 ng/mL）以及霉酚酸酯（2 g/天）。前10例患者在移植后第0天和第14天接受达利珠单抗（2 mg/kg）诱导治疗。由于急性排斥反应发生率高，后15例患者的方案进行了修改，包括在移植后第0天和第2天接受兔抗人胸腺细胞免疫球蛋白（1.5 mg/kg）的T细胞清除抗体诱导治疗，随后在术后第14天接受达利珠单抗治疗。受者纳入标准包括：（1）再次移植受者；或（2）峰值群体反应性抗体（PRA）≥25%的患者。所有排斥反应发作均通过活检诊断，并使用班夫97标准进行分级。
25例患者入组，中位随访时间为402天。40%的受者为黑人，68%的患者为再次移植受者，68%接受了死亡供者肾脏，36%的患者峰值群体反应性抗体（PRA）>25%。在研究期间，总体急性排斥反应、移植物存活率和患者存活率分别为40%、88%和96%。接受达利珠单抗诱导的10例患者中有6例（60%）发生急性排斥反应；然而，引入兔抗人胸腺细胞免疫球蛋白后急性排斥反应发生率降至27%（P = 0.1）。
本研究支持我们之前在早期CSWD患者多变量分析中的观察结果，即多克隆抗体诱导治疗可降低急性排斥反应。高免疫风险患者或许能够以可接受的急性排斥反应发生率接受早期CSWD。
