Vanderwerf B A, Serota A I
Phoenix Transplant Center, Good Samaritan Medical Center, Arizona 85006.
Transplantation. 1988 Feb;45(2):320-3. doi: 10.1097/00007890-198802000-00014.
Low-dose cyclosporine (CsA) plus prednisone for induction and maintenance immunosuppression were used in 106 consecutive cadaveric renal transplants. Previous reports of lower initial CsA have described its use in combination with other forms of immunosuppression. An oral CsA dose of 3 mg/kg was given 2-4 hr before operation, and maintenance CsA was started 12 hr post-operatively at 1 or 1.5 mg/kg i.v. every 12 hr for non-functioning and functioning kidneys, respectively. Oral CsA was given at 3 times the i.v. dose and started 2-3 days postoperatively. The CsA dose was adjusted to maintain plasma trough levels, as measured by radio-immunoassay, of 150-200 ng/ml for the first two weeks, 125-175 ng/ml 2-4 weeks posttransplant, and 100-150 ng/ml for the second month after transplant. Between two and six months, the CsA dose was gradually reduced by 33%. Maintenance prednisone was rapidly reduced 5 mg/month to a maintenance dose of 10 mg/day. Graft survivals for low and high-risk patients at one year were 91% and 81%, respectively. Patient survivals for low-and high-risk patients at one year were 97% and 90%, respectively. Patient death was caused by: aspiration (1), suicide (1), cardiac failure (1), Mediterranean fever with colon perforation (1), and traumatic renal artery disruption (1). Except for death, grafts were lost to primary nonfunction (2), accelerated rejection at +/- 12 hr (3), medical noncompliance (1), renal artery thrombosis (1), and vascular rejection (1). Of 106 patients, 26 (25% were treated for rejection with 3.5 g of i.v. methylprednisolone over 10 days; 25/26 (96%) rejections were reversed with methylprednisolone alone. OKT-3 failed to reverse the remaining vascular rejection. All 9 conversions from CsA to azathioprine for toxicity were successful. Our definition of toxicity was rising serum creatinine, normal CsA level, and no response to 7-10 days of i.v. methylprednisolone and no change in biopsy. We were not able to distinguish CsA toxicity and rejection in most biopsies. Average serum creatinines at 1, 6, and 12 months were 1.6 mg/dl, 1.55 mg/dl and 1.65 mg/dl, respectively. We conclude that low-dose CsA plus prednisone can be successfully used for all cadaveric renal transplants without other forms of immunosuppression. Steroid-resistant rejection is extremely rare if adequate time is given for i.v. methylprednisolone treatment. Almost all "steroid-resistant rejections" were found to be CsA toxicity, and they were reversed after conversion to azathioprine.
106例连续性尸体肾移植采用低剂量环孢素（CsA）加泼尼松进行诱导和维持免疫抑制。先前关于较低初始剂量CsA的报道描述了其与其他免疫抑制形式联合使用的情况。术前2 - 4小时口服CsA剂量为3mg/kg，术后12小时开始维持CsA治疗，无功能肾和有功能肾分别静脉注射1mg/kg或1.5mg/kg，每12小时一次。术后2 - 3天开始口服CsA，剂量为静脉注射剂量的3倍。通过放射免疫测定法调整CsA剂量，以维持血浆谷浓度在前两周为150 - 200ng/ml，移植后2 - 4周为125 - 175ng/ml，移植后第二个月为100 - 150ng/ml。在2至6个月期间，CsA剂量逐渐减少33%。维持泼尼松迅速以每月5mg的速度减量至维持剂量10mg/天。低风险和高风险患者一年时的移植物存活率分别为91%和81%。低风险和高风险患者一年时的患者存活率分别为97%和90%。患者死亡原因包括：误吸（1例）、自杀（1例）、心力衰竭（1例）、地中海热伴结肠穿孔（1例）和创伤性肾动脉破裂（1例）。除死亡外，移植物丢失原因包括原发性无功能（2例）、移植后±12小时加速排斥（3例）、医疗不依从（1例）、肾动脉血栓形成（1例）和血管排斥（1例）。106例患者中，26例（25%）因排斥反应接受了10天内静脉注射3.5g甲泼尼龙治疗；25/26例（96%）排斥反应仅用甲泼尼龙逆转。OKT - 3未能逆转其余的血管排斥反应。所有9例因毒性从CsA转换为硫唑嘌呤的病例均成功。我们对毒性的定义是血清肌酐升高、CsA水平正常、静脉注射甲泼尼龙7 - 10天无反应且活检无变化。在大多数活检中我们无法区分CsA毒性和排斥反应。1个月、6个月和12个月时的平均血清肌酐分别为1.6mg/dl、1.55mg/dl和1.65mg/dl。我们得出结论，低剂量CsA加泼尼松可成功用于所有尸体肾移植，无需其他形式的免疫抑制。如果给予足够时间进行静脉注射甲泼尼龙治疗，激素抵抗性排斥极为罕见。几乎所有“激素抵抗性排斥反应”被发现是CsA毒性，转换为硫唑嘌呤后得以逆转。
