Cantarovich D, Giral-Classe M, Hourmant M, Dantal J, Blancho G, Lerat L, Moreau A, Soulillou J P
Department of Nephrology and Clinical Immunology, Institut de Transplantation et de Recherche en Transplantation (ITERT), Nantes, France.
Nephrol Dial Transplant. 2000 Oct;15(10):1673-6. doi: 10.1093/ndt/15.10.1673.
Despite their well-known side-effects, corticosteroids (Cs) are currently used after kidney transplantation. Avoidance of Cs may improve patient quality of life and eventual long-term survival. We report on a regimen using antithymocyte globulin (ATG) and mycophenolate mofetil (MMF) for induction, and cyclosporin (CsA) plus MMF for maintenance treatment of recipients of primary kidney transplantation.
We studied 11 consecutive, non-sensitized renal transplant patients (nine cadaver and two living donors). Initial immunosuppression consisted of ATG (1.5 mg/kg/day, i.v.) given for 10 days and MMF (1.0 g/b.i.d.). CsA (8 mg/kg, in two divided doses) was started on post-operative day 11. Cs were only allowed in the case of MMF discontinuation, for the treatment of acute rejection, and in the event of recurrence of the primary glomerulonephritis.
All patients completed the entire 10-day ATG course. Main side-effects included fever (>38 degrees C) and serum sickness, observed in 73 and 27% of the patients respectively. The incidence of acute rejection was 27% (three of 11 patients). In two patients with acute rejection, serum sickness was concomitantly diagnosed and renal histology was partially compatible with immune-complex disease. The remaining patient had two episodes of low-grade rejection. All rejection episodes were rapidly reversed. Two patients (18%) were treated with ganciclovir for cytomegalovirus (CMV) infection. Two patients (18%) are currently receiving Cs for recurrence of the native glomerulonephritis and two rejection episodes respectively. All patients are currently alive with functioning kidneys (average follow-up of 8.4 months; average creatinine level of 128 micromol/l).
This pilot study suggests that ATG induction in combination with MMF and delayed introduction of CsA, in the absence of Cs, is not well tolerated in recipients of kidney transplants. An earlier introduction of calcineurin inhibitors and/or a shorter course of ATG may reduce the incidence of fever and serum sickness secondary to ATG.
尽管皮质类固醇(Cs)存在众所周知的副作用,但目前仍用于肾移植术后。避免使用Cs可能会改善患者的生活质量并最终提高长期生存率。我们报告了一种方案,该方案使用抗胸腺细胞球蛋白(ATG)和霉酚酸酯(MMF)进行诱导,并使用环孢素(CsA)加MMF对初次肾移植受者进行维持治疗。
我们研究了11例连续的、未致敏的肾移植患者(9例尸体供肾和2例活体供肾)。初始免疫抑制包括给予ATG(1.5mg/kg/天,静脉注射)10天和MMF(1.0g,每日两次)。术后第11天开始使用CsA(8mg/kg,分两次给药)。仅在停用MMF、治疗急性排斥反应以及原发性肾小球肾炎复发的情况下才允许使用Cs。
所有患者均完成了为期10天的ATG疗程。主要副作用包括发热(>38摄氏度)和血清病,分别在73%和27%的患者中观察到。急性排斥反应的发生率为27%(11例患者中有3例)。在2例急性排斥反应患者中,同时诊断出血清病,肾组织学与免疫复合物疾病部分相符。其余患者有2次轻度排斥反应发作。所有排斥反应发作均迅速逆转。2例患者(18%)因巨细胞病毒(CMV)感染接受更昔洛韦治疗。2例患者(18%)目前分别因原发性肾小球肾炎复发和2次排斥反应发作而接受Cs治疗。所有患者目前均存活且肾脏功能良好(平均随访8.4个月;平均肌酐水平为128微摩尔/升)。
这项初步研究表明,在不使用Cs的情况下,肾移植受者对ATG诱导联合MMF以及延迟引入CsA的耐受性不佳。更早引入钙调神经磷酸酶抑制剂和/或缩短ATG疗程可能会降低ATG继发的发热和血清病的发生率。