雷帕霉素治疗肾移植术后慢性移植物肾病疗效的初步观察  

Therapeutic effect of sirolimus against chronic allograft nephropathy in kidney transplant recipients

作　　者：王长希[1] 陈思阳[1] 陈立中[1] 刘龙山[1] 费继光[1] 邓素雄[1] 邱江[1] 李军[1] 郑克立[1] 吴培根[2] 纪玉莲[2] 朱兰英[2] 

机构地区：[1]中山大学附属第一医院器官移植中心,广东广州510080 [2]中山大学附属第一医院肾科,广东广州510080

出　　处：《南方医科大学学报》2007年第12期1924-1926,共3页Journal of Southern Medical University

摘　　要：目的探讨雷帕霉素对肾移植术后慢性移植物肾病(CAN)的疗效和安全性。方法回顾性分析2002年3月起在本中心随访的31例CAN患者的临床资料,比较从钙神经蛋白抑制剂(CNI)为主的方案转换成SRL为主的方案前后的血清肌酐值(Cr)变化,统计用药相关的不良反应。结果15名患者达到主要终点即恢复规律透析,8人肾功能改善,8人肾功能维持。其中高Cr0组(Cr0≥3mg/dl,n=12)有9人恢复透析,两人肾功能改善;低Cr0组(Cr0<3mg/dl,n=19)中5人恢复透析,8人肾功能维持,6人肾功能改善;两亚组间有显著差异(P=0.003)。14人到达次要终点即停用SRL,其中5人因感染停用SRL,最终4人恢复透析,1人死于感染;9人因不良反应停用SRL改用其他免疫抑制剂,后4人恢复透析,2人肾功能维持,3人肾功能改善。高脂血症(51.6%)、白细胞减少(41.9%)、口腔溃疡(29.0%)和肝功能损害(16.1%)是本研究中SRL常见的不良反应。严重不良事件共13人次,包括脑出血死亡2例、感染死亡3例和需要住院治疗的肺部和泌尿道感染共8人次。结论CNI转换为SRL对部分CAN患者有效,在基线肌酐水平低于3mg/L的患者尤其明显;但SRL的应用必需注意高脂血症和白细胞减少等不良反应及其相关的脑血管意外和感染。Objective To investigate the efficacy and safety of sirolimus in management of chronic allograft nephropathy （CAN）. Methods A retrospective study was conducted involving 31 CAN patients followed up since March 2002, who experienced a change from a calcineurin inhibitor （CNI）-based regimen to a SRL-based regimen. Serum creatinine （Cr） in these patients was compared before and after the regimen change, and the adverse events associated with SRL were analyzed. Results Till March 2007 when the study closed, 15 patients reached the primary endpoint for resuming dialysis, 8 had improved and 8 had stable renal function. In patients with high Cr0（≥3 mg/L, n=12）, 9 resumed dialysis and 2 had improved renal function, but one of the patients with renal improvement eventually died due to infection; in the patients with low Cr0 （〈3 mg/L, n=19）, 5 resumed dialysis, 8 had stable renal function and 6 had improved renal function, showing significant difference between the 2 groups （P=0.003）. Altogether 14 patients reached the secondary endpoint for ceasing SRL for severe infection （5 patients, of whom 4 resumed dialysis and 1 died of infection） or adverse events associated with SRL （9 patients, of whom 4 resumed dialysis, 2 had stable and 3 had improved renal function）. Hyperlipidemia （51,6%）, leukocytopenia （41.9%）, mouth ulcer （29.0%） and liver function lesion （16.1%） were the commonest adverse events in these patients, and totalling 13 severe adverse events were recorded, including 2 fatal cerebral hemorrhage, 3 fatal infection episodes, and 8 pulmonary and urinary infections that require hospitalization. Conclusions Conversion from a CNI-based to SRL-based regimen can be effective for some CAN cases, especially for those with Cr0 below 3 mg/L. Attention must be given to adverse events like hyperlipidemia and leukocytopenia, as well as the related cerebral vascular accidents and infections.

关 键 词：雷怕霉素 慢性移植物肾病 钙神经蛋白抑制剂 肾移植 

分 类 号：R699[医药卫生—泌尿科学] R692[医药卫生—外科学]