Department of Medicine, McGill University Health Center, Montreal, Quebec, Canada.
Transplantation. 2013 Feb 15;95(3):495-500. doi: 10.1097/TP.0b013e318277230e.
Chronic kidney disease (CKD) is a frequent complication after liver transplantation (LT) and is associated with increased mortality. Strategies to reduce calcineurin inhibitor (CNI) dose or conversion to either mycophenolate mofetil and/or rapamycin resulted in variable results and side-effect profiles.
We evaluated the effectiveness of CNI conversion to long-term anti-CD25 monoclonal antibody (mAb)-based immunosuppression in 15 adult LT patients with CKD at 7.6±4 years posttransplant (intervention group). Three patients had been previously switched to rapamycin, and 12 patients were on CNI. The control group included 15 LT patients on CNI with stable renal function over a similar posttransplant follow-up period.
Anti-CD25 mAb were given over a period of 26±15 months (range, 2-51 months) and were well tolerated. The slope of calculated creatinine clearance was -0.66 mL/min/month over 6 months before conversion and -0.05 mL/min/month after conversion to anti-CD25 mAb (P=0.16 and P=0.86 vs. controls). Three acute rejection episodes occurred in the intervention group. Acute rejection was reversible in two patients. However, one patient died of chronic rejection 1 year after having been switched to tacrolimus. Anti-CD25 mAb were replaced with either CNI or rapamycin in six patients (acute rejection [n=2], progression to end-stage renal disease [n=2], poor venous status [n=1], increased liver enzymes [n=1]).
The use of long-term anti-CD25 mAb therapy as a replacement to CNI and rapamycin-based immunosuppression may be feasible. It is crucial that rejection surveillance is intensified. A randomized controlled trial is required to confirm the benefits of this strategy.
慢性肾病（CKD）是肝移植（LT）后的常见并发症，与死亡率增加有关。减少钙调神经磷酸酶抑制剂（CNI）剂量或转换为霉酚酸酯和/或雷帕霉素的策略导致了不同的结果和副作用。
我们评估了在 15 例 LT 后 CKD 患者（7.6±4 年）中，将 CNI 转换为长期抗 CD25 单克隆抗体（mAb）为基础的免疫抑制的有效性。其中 3 例患者之前已转换为雷帕霉素，12 例患者正在使用 CNI。对照组包括 15 例 LT 患者，在相似的移植后随访期间，CNI 治疗时肾功能稳定。
抗 CD25 mAb 治疗持续了 26±15 个月（范围 2-51 个月），耐受性良好。转换前 6 个月估算的肌酐清除率斜率为-0.66mL/min/月，转换后为-0.05mL/min/月（P=0.16 和 P=0.86 与对照组比较）。干预组发生 3 例急性排斥反应。在 2 例患者中，急性排斥反应是可逆的。然而，1 例患者在转换为他克莫司后 1 年因慢性排斥反应而死亡。在 6 例患者中（急性排斥反应[2 例]、进展至终末期肾病[2 例]、静脉状态差[1 例]、肝酶升高[1 例]），抗 CD25 mAb 被 CNI 或雷帕霉素取代。
长期使用抗 CD25 mAb 作为 CNI 和雷帕霉素为基础的免疫抑制的替代物可能是可行的。加强排斥反应监测至关重要。需要进行随机对照试验来证实这一策略的益处。
