Grinyó J M, Gil-Vernet S, Seron D, Hueso M, Fulladosa X, Cruzado J M, Moreso F, Fernandez A, Torras J, Riera L, Castelao A M, Alsina J
Department of Nephrology, Hospital de Bellvitge, CSUB, University of Barcelona, Spain.
Nephrol Dial Transplant. 1998 Oct;13(10):2601-4. doi: 10.1093/ndt/13.10.2601.
In renal transplantation the beneficial immunosuppressive effects of cyclosporin (CsA) may be curtailed by its nephrotoxicity, specially in patients receiving a cadaveric allograft from suboptimal donors or at risk of delayed graft function. Mycophenolate mofetil (MMF) and antithymocyte globulin (ATG) have each demonstrated to be potent immunosuppressants in renal transplantation. In a prospective analysis we have studied the results at 6 months of the combination of MMF, ATG and low-dose steroids in patients with low immunological risk receiving a first cadaveric renal allograft from a suboptimal donor or at risk of delayed graft function.
Patients with preformed reactive antibodies < 500% receiving a first graft from a suboptimal donor (age > or = 40 years, non-heart-beating, acute renal failure, arterial hypertension) or at risk of delayed graft function (cold ischaemia time > or = 24 h) were eligible for this open single-arm pilot trial. From September 1996 to March 1997 we recruited 17 patients. They were treated with MMF 2 g p.o. preoperatively, and after transplantation at 3 g/day; rabbit ATG i.v. at 2 mg/kg preoperatively, and 1.5 mg/kg/day the first day after transplantation, followed by four doses of 1 mg/kg on alternate days; prednisone was given at 0.25 mg/kg/day and reduced progressively to 0.1 mg/kg/day at 3 months. Primary outcomes were incidence of biopsy-proven acute rejection, delayed graft function, opportunistic infections, graft and patient survival, and the need for introduction of CsA treatment.
delayed graft function occurred in two cases (12%). Four of 17 patients (24%) had a biopsy-proven acute rejection (2 grade I and 2 grade II) within the first 3 months after transplantation. CsA was added in two cases with grade II biopsy-proven acute rejection, and in one with grade I biopsy-proven acute rejection. In one patient MMF was replaced by CsA because of gastrointestinal intolerance. Mean serum creatinine 6 months after transplantation was 159+/-59 micromol/1. Cytomegalovirus tissue invasive disease occurred in one patient (6%). At 6 months follow-up all patients are alive with functioning allografts.
These preliminary results suggest that in low-immunological-risk patients who receive a suboptimal renal allograft or at risk of delayed graft function, the combination of MMF, ATG, and steroids is an efficient immunosuppressive regime that may avoid the use of CsA in 70% of the recipients.
在肾移植中，环孢素（CsA）有益的免疫抑制作用可能会因其肾毒性而受到限制，特别是在接受来自非最佳供体的尸体同种异体移植物或有移植肾功能延迟风险的患者中。霉酚酸酯（MMF）和抗胸腺细胞球蛋白（ATG）在肾移植中均已证明是有效的免疫抑制剂。在一项前瞻性分析中，我们研究了MMF、ATG和低剂量类固醇联合应用于免疫风险较低、接受来自非最佳供体的首例尸体肾移植或有移植肾功能延迟风险患者6个月时的结果。
预先存在的反应性抗体<500%、接受来自非最佳供体（年龄≥40岁、非心脏骤停供体、急性肾衰竭、动脉高血压）的首例移植物或有移植肾功能延迟风险（冷缺血时间≥24小时）的患者符合这项开放单臂试验。从1996年9月至1997年3月，我们招募了17例患者。他们术前口服MMF 2 g，移植后每天3 g；术前静脉注射兔ATG 2 mg/kg，移植后第一天1.5 mg/kg/天，随后隔天4次给予1 mg/kg；泼尼松以0.25 mg/kg/天给予，3个月时逐渐减至0.1 mg/kg/天。主要结局为活检证实的急性排斥反应发生率、移植肾功能延迟、机会性感染、移植物和患者生存率，以及引入CsA治疗的必要性。
2例（12%）发生移植肾功能延迟。17例患者中有4例（24%）在移植后前3个月内发生活检证实的急性排斥反应（2例I级和2例II级）。2例II级活检证实的急性排斥反应患者和1例I级活检证实的急性排斥反应患者加用了CsA。1例患者因胃肠道不耐受将MMF换为CsA。移植后6个月时平均血清肌酐为159±59 μmol/L。1例患者（6%）发生巨细胞病毒组织侵袭性疾病。在6个月的随访中，所有患者均存活且移植肾功能良好。
这些初步结果表明，对于接受非最佳肾移植或有移植肾功能延迟风险的低免疫风险患者，MMF、ATG和类固醇联合应用是一种有效的免疫抑制方案，70%的受者可能无需使用CsA。
