心脏移植术后慢性肾功能不全患者应用西罗莫司的经验  

Sirolimus use in heart transplantation recipients with chronic renal dysfunction

作　　者：尹栋[1] 黄洁[1] 丰雷[1] 廖中凯[2] 冯广迅[1] 王巍[2] 宋云虎[2] 胡盛寿[2] 

机构地区：[1]中国医学科学院北京协和医学院阜外心血管病医院心内科,100037 [2]中国医学科学院北京协和医学院阜外心血管病医院心外科,100037

出　　处：《中华心血管病杂志》2012年第2期136-140,共5页Chinese Journal of Cardiology

摘　　要：目的 评价西罗莫司对心脏移植术后出现慢性肾功能不全患者肾功能的影响,并对使用西罗莫司的经验做一个总结.方法 回顾性分析2004年6月至2008年12月在阜外心血管病医院成功接受心脏移植的138例患者的临床资料,共有20例患者由于术后钙调素抑制剂（环孢素及他克莫司）相关的慢性肾功能不全,而加用西罗莫司并减少钙调素抑制剂剂量.换药前,三联维持免疫治疗方案为：泼尼松＋环孢素或他克莫司＋霉酚酸酯或硫唑嘌呤.换药后,加用西罗莫司0.75 ～1.50 mg/d,目标谷浓度为5～15μg/L；同时降低钙调素抑制剂剂量,使血药浓度降至原目标浓度的1/2 ～2/3.换药后,监测血清肌酐、尿素氮、西罗莫司、环孢素及他克莫司水平,同时监测血常规、生化指标以及临床症状了解药物不良反应.常规于术后3周、3个月、6个月、12个月各行1次心内膜活检以监测排异反应,术后1年内的患者在换药后3个月行心内膜活检,术后1年以上的患者在临床怀疑排异反应时行心内膜活检,同时监测超声心动图.结果 换药后随访（7.9±6.3）个月.西罗莫司剂量为（0.89±0.22） mg/d,血药浓度为（7.6±3.8） μg/L.18例患者采用环孢素,剂量从（191.7±60.0） mg/d减少至（123.6±34.8）mg/d,谷值血药浓度从（175.5±58.0） μg/L下降至（111.9±56.0）μg/L（P ＜0.01）；2例患者采用他克莫司,剂量从平均4.25 mg/d减少至3.00 mg/d,谷值血药浓度从13.5 μg/L减少至10.5 μg/L.换药后1个月,血清肌酐从（160.4±25.5） μmol/L下降至（134.4±26.8）μmol/L（P＜0.01）,尿素氮从（13.8±4.7）μmol/L下降至（10.4±3.0） μmol/L（P ＜0.01）.11例术后1年内使用西罗莫司者,共进行了心内膜活检22例次,其中2级排异反应（ISHLT分级）4例次.全部患者均存活,超声心动图提示心功能均无明显异常.换药后1个月,甘油三酯、总胆固醇、低密度脂蛋白胆固醇与换药前比较均Objective To observe the effect of sirolimus-based immunosuppression administered on heart transplant recipients with chronic renal dysfunction.Methods From June 2004 to December 2008,standard calcineurin inhibitors（ CNI）-based immunosuppressive regimen was changed to reduced-dose CNI plus sirolimus due to CNI-related chronic renal dysfunction in 20 out of 138 cardiac transplant recipients at Fuwai Hospital. The standard immunosuppressive regimen included steroid, CNI （cyclosporine or tacrolimus）,and mycophenolate mofetil or azathioprine. Sirolimus was started at 0.75 - 1.50 mg/d with titration to achieve levels of 5 -15 μg/L,and CNI dose was reduced gradually to 1/2 -2/3 of the baseline level.Patients were followed for changes in renal function,lipid level and clinical side effects related to immunosuppressive therapy.Endomyocardial biopsy （EMB） was performed routinely at 3 weeks,3,6 and 12 months after transplantation.EMB was also performed at 3 months after regimen change within 1 year post-transplantation or when rejections were suspected in patients beyond 1 year post-transplantation.Echocardiography was performed for monitoring purpose.Results The mean follow-up after regimen change was （7.9 ±6.3） months.Final sirolimus dose was （0.89 ± 0.22） mg/d and blood drug level was （7.6 ±3.8 ） μg/L.Cyclosporine dose was reduced from （ 191.7 ± 60.0） mg/d to （ 123.6 ± 34.8 ） mg/d,with blood drug concentation reduced from （ 175.5 ± 58.0） μg/L to （ 111.9 ± 56.0） μg/L in 18 patients （ P 〈 0.01 ）.Tacrolimus average dose was reduced from 4.25 mg/d to 3.00 mg/d,with blood drug concentation reduced from 13.5 μg/L to 10.5 μg/L in 2 patients.Serum creatinine level fell from （ 160.4 ± 25.5 ） μmol/L to （ 134.4 ± 26.8 ） μmol/L （ P 〈 0.01 ） and urea nitrogen fell from （ 13.8 ± 4.7 ） μmol/L to （ 10.4±3.0 ）μmol/L（P 〈0.01 ）at one month after regimen change.Twenty two EMBs were performed in 11 patients within 1 year post-transplant,there were

关 键 词：心脏移植 肾功能不全 西罗莫司 

分 类 号：R654.2[医药卫生—外科学]