亲属活体供肾移植后低剂量钙调蛋白酶抑制剂的应用

背景:亲属活体肾移植供、受者移植前准备充分,供肾热、冷缺血时间较短,HLA 配型的组织相容性好,移植后排斥反应发生率低,为亲属活体供肾肾移植后采用低剂量免疫抑制剂方案提供了可能性.目的:探讨亲属活体供肾移植后低剂量钙调蛋白酶抑制剂的安全性和有效性.方法:选取2006-01/2008-06 在南京医科大学第一附属医院肾移植中心行亲属活体供肾移植的受者38 例,移植后常规使用环孢素A/他克莫司+吗替麦考酚酯+泼尼松的三联免疫抑制方案.将38 例患者随机分为两组:CNI 常规剂量组(n=18),移植后初始药物剂量为环孢素A 6 mg/(kg·d)或他克莫司0.12 mg/(kg·d);CNI 低剂量组(n=20),术后初始药物剂量为环孢素A 4 mg/(kg·d)或他克莫司0.08 mg/(kg·d);两组吗替麦考酚酯和泼尼松使用剂量相同.移植后密切随访,比较两组患者移植后不同时期的肾功能以及急性排斥反应、肺部感染、肝功能损害、肾毒性等并发症的发生情况.结果与结论:随访12 个月,CNI 常规剂量组重度肺部感染死亡1 例,CNI 低剂量组无死亡病例.两组移植肾功能及急性排斥反应发生率比较差异均无显著性意义(P ＞ 0.05);CNI 低剂量组肝功能损害、钙调蛋白酶抑制剂肾毒性发生率显著低于CNI 常规剂量组(P ＜ 0.05).此外,采用低剂量钙调蛋白酶抑制剂免疫抑制方案明显减轻了亲属肾移植患者的经济负担.说明亲属活体供肾移植后采用低剂量钙调蛋白酶抑制剂的免疫抑制剂方案安全、有效.

Application of low-dose calcineurin inhibitors in living-related donor renal transplantation

BACKGROUND: Adequate preparation of donors and recipients prior to living-related donor renal transplantation, short warm and cold ischemia time for donor kidney, good histocompatibility of human leukocyte antigen match, and low postoperative rejection incidence provide feasibility for use of low-dose immunosuppressive agents after living-related donor renal transplantation. OBJECTIVE: To investigate the safety and effectiveness of low-dose calcineurin inhibitors (CNI), an immunosuppressive agent, in living-related donor renal transplantation. METHODS: A total of 38 recipients who underwent living-related donor renal transplantation at the Center of Renal Transplantation of the First Affiliated Hospital of Nanjing Medical University from January 2006 to June 2008 were randomized for treatment with mycophenolate mofetil (750 mg twice a day), prednisone, and either standard-dose CNI (n=18) or low-dose CNI (n=20) during 12 months post-transplantation. Ciclosporin A was given orally (starting dose, 6 and 4 mg/kg per day, respectively) in two divided doses to achieve the 12-hour whole blood concentration as measured by fluorescence polarization immunoassay. The starting dose of tacrolimus was 0.12 and 0.08 mg/kg per day respectively, and its whole blood concentration was measured by enzyme-multiplied immunoassay technique. After transplantation, patients were followed up. Renal function, pulmonary infection, liver dysfunction, and CNI nephrotoxicity at different time periods were compared between different regimens. RESULTS AND CONCLUSION: During 12 months post-transplantation, patient death occurred in one of 18 patients (5.6%) in the CNI standard-dose group and none of 20 patients (0%) in the CNI low-dose group. There was no significant difference in renal function and acute rejection between CNI standard-dose and CNI low-dose groups (P > 0.05). The incidence of liver dysfunction and CNI nephrotoxicity was significantly lower in the CNI low-dose group than in the CNI standard-dose group (P < 0.05). In addition, a low-dose CNI regimen helped recipients to lessen the economic burdens. These findings indicate that it is effective, safe and economical to use a low-dose CNI regimen in living-related donor renal transplantation.