钙调磷酸酶抑制剂转换为西罗莫司治疗慢性移植物肾病的疗效研究

Effect of conversion from calcineurin inhibitor to sirolimus on chronic allograft nephropathy

目的探讨钙调磷酸酶抑制剂(CNI)转换为西罗莫司治疗慢性移植物肾病(chronic allograft nephropathy,CAN)的疗效及不良反应。方法回顾性研究对象为2005年1月至2010年12月在西安交通大学医学院第一附属医院肾移植科随访的95例肾移植后并发CAN患者,术后均接受CNI为主的免疫抑制剂方案。所有患者均签署知情同意书,符合医学伦理学规定。患者确诊CAN后将CNI转换为西罗莫司。记录西罗莫司的维持剂量及血药浓度水平,了解转换治疗后血清肌酐(Scr)的变化,根据转换前Scr水平高低分为两组,Scr≥266μmol/L为Scr高水平组(22例),Scr<266μmol/L为Scr低水平组(73例);比较两组转换治疗后Scr变化幅度的差异;了解转换治疗的不良反应。结果 95例患者的随访时间6～48个月,西罗莫司的维持剂量为0.5～4mg/d(中位数为1.5mg/d),血药浓度为1.3～12ng/ml(中位数为5.4ng/ml)。Scr低水平组转换治疗效果明显高于Scr高水平组(P<0.05)。95例患者均未发生急性排斥反应。新发或蛋白尿加重32例(34%),新发或高脂血症加重25例(26%),1例患者发生肺部感染,经对症治疗后均治愈或缓解。结论 CNI类药物转换为西罗莫司治疗CAN是安全有效的,转换前Scr水平较低者的治疗效果优于转换前Scr水平较高者,转换后的主要并发症是蛋白尿和高脂血症。

Objective To investigate the efficacy and adverse reaction of conversion from calcineurin inhibitors （CNI） to sirolimus for treatment of chronic allograft nephropathy（CAN）. Methods The objects of retrospective study were 95 recipients who developed CAN after renal transplantation and were followed up from January 2005 to December 2010 in Department of Renal Transplantation of the First Affiliated Hospital of Medical College of Xi＇ an Jiaotong University. The patients all received the immunosuppressant regimen based on CNI after transplantation. This study was approved by local ethical committee and the informed consent of all participating subjects was obtained. After diagnosis of CAN, the immunosuppressant was changed from CNI to sirolimus. The maintenance dose and blood concentration of sirolimus were recorded. The change of serum creatinine （Scr） level was observed after conversion treatment. Patients were divided into high Scr level group （Scrμ 266 μmol/L, n = 22） and low Scr level group （ Scr 〈 266μmol/L, n = 73 ） before conversion. The difference of change amplitude of Scr level was compared between 2 groups after conversion treatment. The adverse reaction of conversion treatment was observed. Results Follow-up time of 95 patients ranged μom 6 to 48 months. The median of maintenance dose and concentration of sirolimus were 1.5 mg/d （range from 0.5 to 4 mg/d） and 5.4 ng/ml （range from 1.3 to 12 ng/ml） , respectively. The effect of conversion treatment in low Scr level group was significantly better than that in high Scr level group （ P 〈 0. 05 ）.None suffered from acute rejection. Thirty-two cases developed de novo or exacerbated proteinuria （ 34% ） , 25 cases developed de novo or exacerbated hyperlipidemia （26%） were the commonest adverse events, and 1 case developed pulmonary infection. All the patients were cured or relieved after symptomatic treatment. Conclusions It is safe and effective to convert the immunosuppressant from CNI to sirolimus for the treatment of CAN. The effect of conversion treatment in low Scr level group is significantly higher than that in high Scr level group. The major complications are proteinuria and hyperlipidemia.