西罗莫司联合低剂量钙调磷酸酶抑制剂在扩大标准供者供肾移植中的临床研究

Clinical study ofsirolimus plus low-dose calcineurin inhibitor after kidney transplantation from expanded criteria donors

目的探讨扩大标准供者供肾移植术后由传统钙调磷酸酶抑制剂为基础的免疫抑制方案转换为西罗莫司联合低剂量钙调磷酸酶抑制剂方案的有效性和安全性。方法前瞻性、开放性、非随机的临床对照研究,选取2017年6月至2018年3月在北京友谊医院接受首次肾移植手术(供肾均为扩大标准供者供肾)并于术后3个月转换为西罗莫司联合低剂量钙调磷酸酶抑制剂方案的受者15例。所有受者均完成1年随访,观察移植肾存活时间,转换前、后(0、1、3、6、12个月)的血肌酐及肾小球滤过率变化,转换前、后尿蛋白的变化,同时记录转换后急性排斥反应发生率、BK病毒、巨细胞病毒感染情况和西罗莫司相关并发症。结果15例受者在转换方案后肾功能均有不同程度改善,移植肾1年存活率100%(15/15)。转换后1、3个月血肌酐下降及肾小球滤过率升高明显(P<0.05)。5例受者转换方案前尿BK病毒阳性,转换方案后3例受者均于3个月内BK病毒转阴,其余2例受者尿BK病毒载量也较前下降。转换方案后,仅2例受者(13.3%)新发轻度蛋白尿。8例受者(53.3%)新发不同程度的高甘油三酯血症,且均能通过药物控制在可接受范围。所有受者在治疗和随访期间均未发生急性排斥反应。结论西罗莫司联合低剂量钙调磷酸酶抑制剂对于扩大标准供者供肾移植受者是一种安全有效的治疗方案,尤其针对早期肾功能恢复欠佳的受者,但是该方案并不能完全取代传统的免疫抑制方案,需合理选择受者,进行个体化治疗。

Objective To explore the efficacy and safety of converting from traditional calcineurin inhibitor-based immunosuppressive regimen to sirolimus plus low-dose calcineurin inhibitor after kidney transplantation from expanded criteria donors.Methods For this prospective,open-label,non-randomized controlled clinical trial,15 recipients of initial transplant from expanded criteria donors received sirolimus plus low-dose calcineurin inhibitor regimen 3 months after transplantation during June 2017 and March 2018.The follow-up period was over 1 year.The allograft survival time,changes in blood creatinine and glomerular filtration rate before and after conversion(0,1,3,6,12 months),changes in urinary protein before and after conversion,incidence of acute rejection after conversion,BK virus or cytomegalovirus infection and sirolimus-related complications were observed.Results Renal functions of all 15 patients improved after conversion and 1-year allograft survival rate was 100%(15/15).Serum creatinine decreased markedly and glomerular filtration rate increased significantly at 1 month and 3 months after conversion(P<0.05).BK viruria was detected in 5 patients before conversion.After conversion,BK virus turned into negative in 3 patients within 3 months and viral load also decreased in another 2 patients.After conversion,only 2 patients(13.3%)developed de novo proteinuria.Eight patients(53.3%)developed de novo hypertriglyceridemia responding well to medications.None of them experienced acute rejection during follow-ups.Conclusions Sirolimus plus low-dose calcineurin inhibitor is a safe and effective maintenance immunosuppressive regimen for recipients of kidneys from expanded criteria donors,especially for those with abnormal renal function during recovery.But it cannot completely replace the traditional immunosuppressive regimen.Individualized treatment should be chosen properly for recipients.