Bakr Mohamed Adel, Nagib Ayman Maher, Gheith Osama Ashry, Hamdy Ahmed Farouk, Refaie Ayman Fathi, Donia Ahmed Farouk, Neamatalla Ahmed Hassan, Eldahshan Khaled Farouk, Denewar Ahmed Abdelfattah, Abbas Mohamed Hamed, Mostafa Amany Ismail, Ghoneim Mohamed Ahmed
Department of Dialysis and Transplantation, The Urology and Nephrology Center, Mansoura University, Egypt.
Exp Clin Transplant. 2017 Feb;15(Suppl 1):16-23. doi: 10.6002/ect.mesot2016.L46.
We review different immunosuppressant protocols used for living-donor kidney transplant recipients at our center.
Many prospective randomized studies from our center have been reported between March 1976 and 2016, with more than 2700 renal transplant procedures conducted. The first study was a prospective randomized trial of azathioprine versus cyclosporine. The second study compared triple therapy (prednisolone + azathioprine + cyclosporine) versus conventional therapy (prednisolone + azathioprine). The third study was a cost-saving study, in which 100 patients received ketoconazole along with the triple regimen. Another trial demonstrated the advantages of a microemulsion form of cyclosporine. A subsequent trial compared calcineurin inhibitor minimization versus avoidance protocols. Rescue therapies were carried out to intensify immunosuppressive regimens after repeated rejection. In addition, steroid-free regimens were evaluated during both short- and long-term treatment. A recent trial reported a step-forward avoidance protocol with a calcineurin inhibitor and a steroid-free regimen, whereas another current study is the TRANSFORM one. The rationale behind antibody therapy was tho roughly evaluated among living-donor renal trans plant recipients with different agents, including basiliximab, daclizumab, antithymocyte globulin, and alemtuzumab.
Earlier studies have demonstrated the efficacy of conventional regimens without induction therapy, especially in longer follow-up. The standard triple therapy has emerged with intensified immunosuppressive and lowered dose of each drug, especially cyclosporine. In minimization studies, no significant differences were encountered regarding patient and graft survival, even in the long-term. Steroid avoidance was safe and effective. Calcineurin inhibitors and steroid-free regimens have shown comparable patient and graft survival. Induction therapy has lowered the incidence and severity of acute rejection.
A better 5-year graft survival and less posttransplant complications have been achieved with steroid avoidance after induction with basiliximab. Induction therapy did not affect graft and patient survival rates despite lowered incidence and severity of acute rejections.
我们回顾了本中心用于活体供肾移植受者的不同免疫抑制方案。
1976年3月至2016年间，本中心报告了多项前瞻性随机研究，共进行了2700多例肾移植手术。第一项研究是硫唑嘌呤与环孢素的前瞻性随机试验。第二项研究比较了三联疗法（泼尼松龙+硫唑嘌呤+环孢素）与传统疗法（泼尼松龙+硫唑嘌呤）。第三项研究是一项成本节约研究，100名患者在三联疗法中加用酮康唑。另一项试验证明了环孢素微乳剂的优势。随后的一项试验比较了钙调神经磷酸酶抑制剂最小化方案与避免方案。在反复发生排斥反应后，采用挽救疗法强化免疫抑制方案。此外，在短期和长期治疗中均对无类固醇方案进行了评估。最近一项试验报告了一种使用钙调神经磷酸酶抑制剂和无类固醇方案的前瞻性避免方案，而另一项当前研究是TRANSFORM研究。在使用包括巴利昔单抗、达利珠单抗、抗胸腺细胞球蛋白和阿仑单抗在内的不同药物的活体供肾移植受者中，对抗体治疗的基本原理进行了全面评估。
早期研究表明，无诱导治疗的传统方案有效，尤其是在更长时间的随访中。标准三联疗法出现，免疫抑制作用增强，每种药物尤其是环孢素的剂量降低。在最小化研究中，即使在长期，患者和移植物存活率方面也未发现显著差异。避免使用类固醇是安全有效的。钙调神经磷酸酶抑制剂和无类固醇方案在患者和移植物存活率方面表现相当。诱导治疗降低了急性排斥反应的发生率和严重程度。
在使用巴利昔单抗诱导后避免使用类固醇，5年移植物存活率更高，移植后并发症更少。尽管急性排斥反应的发生率和严重程度降低，但诱导治疗并未影响移植物和患者存活率。
