西罗莫司在肾移植术后远期各类并发症患者中的转换应用

目的 探讨以钙调磷酸酶抑制剂(CNI)为主要免疫抑制方案的肾移植受者术后远期发生各类并发症时,应用两罗莫司(SRL)转换治疗方案的有效性及安全性.方法 肾移植术后远期38例采用CNI的患者因发生各类并发症而转换为SRL治疗,其中慢性移植肾肾病(CAN)17例、肿瘤10例、糖尿病3例、移植肾动脉狭窄(TRAS)球囊扩张术后2例、CNI毒性肝损害2例、丙型肝炎病毒(HCV)感染2例、面容改变1例及马兜铃酸肾病1例.SRL首剂负荷剂量为4～6 mg,维持剂量为1～2 mg/d,血SRL浓度维持在4～8 μg/L.使用SRL当天,CNI的用量减少一半,并在达到血SRL目标浓度的2～4周内逐渐撤除.转换后对患者随访了3～46个月,动态观察血常规、血肌酐、血糖、血脂及尿蛋白等指标,观察不良反应及监测急性排斥反应、移植肾功能丧失和肺部感染等并发症的发生.结果 转换治疗后.17例CAN患者中12例肾功能明显好转,血肌酐水平由转换前的(195.8±40.0)μmol/L降至(159.1±37.5)μmol/L(P<0.05);10例肿瘤患者中7例存活良好,2例发生肿瘤远处转移,1例死亡,血肌酐水平由转换前的(102.8±28.0)μmol/L降至转换后3个月的(77.8±25.6)μmol/L(P<0.05);2例TRAS球囊扩张术后患者肾功能恢复正常,TRAS未再发生;3例糖尿病患者血糖水平有所改善;2例CNI肝毒性者转换后肝功能恢复正常;2例HCV感染者肝功能稳定,病毒RNA拷贝水平下降;1例面容改变者症状明显好转;1例马兜铃酸肾病者未发生肿瘤.转换治疗后,所有患者均未发生急性排斥反应,不良反应主要为高脂血症3例、蛋白尿3例及白细胞减少1例.结论 肾移植术后采用CNI者发生CAN等远期并发症时,将CNI转换为西罗莫司治疗是安全,有效的.

Application of sirolhnus in renal transplant patients with long-term complications

Objective To evaluate the efficacy and safety of conversion treatment with sirolimus (SRL) in renal transplant patients with various long-term complications.Methods Thirty-eight cases of long-term patients after renal transplantation received conversion treatment with SRL, including 17 eases of chronic allograft nephropathy (CAN), 10 eases of post-transplant tumor, 2 cases of transplant renal artery stenosis (TRAS) after balloon dilation, 3 eases of post-transplant diabetes mellitus, 2 cases of CNI liver toxicity, 2 cases of HCV infection, one case of face change and one ease of aristolochic acid nephropathy.Patients underwent gradual conversion with maintenance at 1-2 mg/ day after first loading dose of 4-6 mg, and the target concentration was 4-8 μg/L.CNI dosage was reduced by half on the first day of SRL conversion and gradually removed in achieving the target concentration of 2 to 4 weeks.Serum creatinine levels and other laboratory indicators, acute rejections, loss of grafts and pulmonary infections were dynamically observed during the follow-up period of 3-46 months.Results After conversion treatment, serum creatinine level in 17 patients with CAN was decreased from (195.8±40.0) μmol/L to (159.1±37.5) μmol/L.Serum creatinine level in 10 patients with tumor was decreased from (102.8±28.0) μmol/L to (77.8±25.6) μmol/L.Seven of them survived well, distant metastasis occurred in 2 eases and 1 patient died.Renal functionreturned to the normal level in 2 cases of ARTS and no restenosis occurred.The blood glucose level in3 cases of post-transplant diabetes was decreased to some extent; the liver function in 2 patients with CNI-induced renal toxicity recovered; the liver function in 2 cases of HCV infection was stable and virus RNA value was decreased; the symptoms in one case of facial change were significantly improved; Tumor was not found during the follow-up in one case of aristolochic acid nephropathy.After conversion treatment, no acute rejection was found, and adverse reactions included hyperlipidemia (3 cases), proteinuria (3 cases) and leucopenia (one case).Conclusion Conversion to SRL-based immunosuppression therapy is safe and effective in renal transplant patients with long-term complications, such as CAN.