Eberhard O K, Kliem V, Oldhafer K, Schlitt H J, Pichlmayr R, Koch K M, Brunkhorst R
Abteilung Nephrologie and Klinik für Abdominal- und Transplantationschirurgie, Medizinische Hochschule Hannover, Germany.
Transplantation. 1996 May 15;61(9):1345-9. doi: 10.1097/00007890-199605150-00010.
Nineteen patients with biopsy-confirmed ongoing acute rejection of renal allografts were converted from standard immunosuppression to FK506. Eight grafts showed vascular rejection and 11 had cellular rejection on biopsy. All patients had already received intravenous high-dose steroid treatment. Ten patients also had additional OKT3 rescue therapy. Initial FK506 doses were 0.13 +/- 0.06 mg/kg/day; the FK506 whole blood trough level after 3 days of treatment was 9.3 +/- 4.5 ng/ml. After conversion to FK506 all but four patients also received azathioprine, 1.5-2 mg/kg/day, and all patients received oral prednisolone. Concomitant with initiation of FK506, an anti-infective prophylaxis was prescribed, consisting of ganciclovir and trimethoprim/sulfamethoxazole. Sixteen out of 19 of the grafts (84%) were rescued successfully, including two grafts of patients already on hemodialysis at the time of conversion. Graft function of the responders improved from an average serum creatinine level of 364 +/- 109 mumol/L to 154 +/- 49 mumol/L. Of the patients receiving high-dose steroids alone prior to FK506 initiation, 8/9 responded to FK506 treatment, compared with 8/10 of those who had also received OKT3. During the mean follow-up of 35 weeks after conversion, no clinically apparent cytomegalovirus infection and no pneumonia were seen. Treatment with FK506 may successfully suppress ongoing acute rejection, even if antilymphocyte preparations have failed. FK506 can be used at a lower dose than so far recommended without impairing the antirejection potential. An additional anti-infective prophylaxis seems effective in preventing severe complications in the first months after rejection therapy.
19例经活检证实存在肾移植急性排斥反应的患者从标准免疫抑制治疗转换为使用FK506治疗。活检显示8例移植肾发生血管性排斥反应，11例为细胞性排斥反应。所有患者均已接受静脉高剂量类固醇治疗。10例患者还接受了额外的OKT3挽救治疗。FK506初始剂量为0.13±0.06mg/kg/天；治疗3天后FK506全血谷浓度为9.3±4.5ng/ml。转换为FK506治疗后，除4例患者外，其余患者均接受了硫唑嘌呤治疗，剂量为1.5 - 2mg/kg/天，所有患者均接受口服泼尼松龙治疗。在开始使用FK506的同时，给予抗感染预防措施，包括更昔洛韦和甲氧苄啶/磺胺甲恶唑。19例移植肾中有16例（84%）成功挽救，其中包括2例在转换治疗时已接受血液透析的患者。反应者的移植肾功能从平均血清肌酐水平364±109μmol/L改善至154±49μmol/L。在开始使用FK506之前仅接受高剂量类固醇治疗的患者中，8/9对FK506治疗有反应，而在同时接受OKT3治疗的患者中，这一比例为8/10。在转换治疗后的平均35周随访期间，未观察到明显的临床巨细胞病毒感染和肺炎。即使抗淋巴细胞制剂治疗失败，使用FK506治疗仍可成功抑制正在进行的急性排斥反应。FK506可使用比目前推荐剂量更低的剂量，而不影响其抗排斥潜力。额外的抗感染预防措施似乎可有效预防排斥反应治疗后最初几个月的严重并发症。
