Suthanthiran M, Haschemeyer R H, Riggio R R, Adubor C, Friedman G S, Cheigh J S, Wang J C, Fotino M, Stubenbord W T, Saal S D
Department of Biochemistry, Rogosin Institute, New York, NY 10021.
Transplantation. 1993 May;55(5):1008-13. doi: 10.1097/00007890-199305000-00011.
Many transplant centers routinely utilize monoclonal antibody or polyclonal antibody based induction protocols in recipients of cadaver renal allografts. Given the potential complications associated with antibody-based immunosuppression regimens (e.g., CMV disease), we tested the hypothesis that a combination of a calcium antagonist and a triple drug protocol (cyclosporine + prednisone + azathioprine) would be an effective substitute for antibody-based induction protocols in ensuring excellent patient and graft survival rates. Our postulate was tested in a prospective study of 52 consecutive recipients of cadaver renal allografts (44 first, 5 second, and 3 third grafts) utilizing nifedipine as the first line calcium antagonist. Nifedipine was selected over verapamil or diltiazem due to its lack of interference with the metabolism of CsA. Some of the significant outcomes of our prospective trial were (A) a cumulative patient survival rate of 98.1% for the 52 recipients at 18 months posttransplantation; (B) a cumulative allograft survival rate of 92.1% for the 52 consecutive cadaver renal allografts at 18 months; (C) a cumulative allograft survival rate of 100% at 18 months for the 24 of 52 renal allografts without delayed graft function following transplantation; and (D) a cumulative allograft survival rate of 86% at 18 months for the 28 of 52 renal allografts with delayed graft function. Of the 4 of 52 who lost their grafts, 2 grafts were removed following discontinuation of immunosuppressive therapy while the remaining 2 had primary nonfunction; and (E) the lack of a requirement for monoclonal or polyclonal antibodies for the treatment of acute rejection episodes in this patient population. These gratifying results compare very favorably with (A) recent reports of the effects of long-term diltiazem therapy and of verapamil used in conjunction with an induction protocol that included Minnesota antilymphocyte globulin in recipients of cadaver renal allografts, and (B) the clinical outcome in many institutions with OKT3/ATG/ALG induction protocols. Whereas the mechanisms involved in the excellent clinical outcome found with the calcium antagonist remain undefined, our results strongly argue for a prospective, randomized and controlled study in which a calcium antagonist-supplemented immunosuppressive regimen is compared with antibody-based induction protocols.
许多移植中心在尸体肾移植受者中常规采用基于单克隆抗体或多克隆抗体的诱导方案。鉴于基于抗体的免疫抑制方案存在潜在并发症（如巨细胞病毒病），我们检验了以下假设：钙拮抗剂与三联药物方案（环孢素+泼尼松+硫唑嘌呤）联合使用，在确保患者和移植物具有优异存活率方面，将是基于抗体的诱导方案的有效替代方案。我们的假设在一项前瞻性研究中得到验证，该研究纳入了52例连续的尸体肾移植受者（44例首次移植、5例第二次移植和3例第三次移植），使用硝苯地平作为一线钙拮抗剂。由于硝苯地平不干扰环孢素的代谢，所以选用它而非维拉帕米或地尔硫䓬。我们前瞻性试验的一些重要结果如下：（A）52例受者在移植后18个月时的累积患者存活率为98.1%；（B）52例连续尸体肾移植在18个月时的累积移植物存活率为92.1%；（C）52例肾移植中有24例移植后无移植功能延迟，其在18个月时的累积移植物存活率为100%；（D）52例肾移植中有28例有移植功能延迟，其在18个月时的累积移植物存活率为86%。在52例中失去移植物的4例受者中，2例在停用免疫抑制治疗后移除了移植物，其余2例存在原发性无功能；（E）该患者群体在治疗急性排斥反应时无需使用单克隆或多克隆抗体。这些令人满意的结果与以下情况相比非常有利：（A）最近关于长期使用地尔硫䓬治疗以及维拉帕米与包括明尼苏达抗淋巴细胞球蛋白在内的诱导方案联合用于尸体肾移植受者的效果的报告；（B）许多采用OKT3/抗胸腺细胞球蛋白/抗淋巴细胞球蛋白诱导方案的机构的临床结果。虽然钙拮抗剂取得优异临床结果所涉及的机制尚不清楚，但我们的结果有力地支持进行一项前瞻性、随机对照研究，将补充钙拮抗剂的免疫抑制方案与基于抗体的诱导方案进行比较。
