钙调磷酸酶抑制剂减量的吗替麦考酚酯免疫抑制方案对改善肝移植术后肾损害的影响  

Mycophenolate mofetil-based calcineurin inhibitor reduced immunosuppressive protocol for the improvement of renal dysfunction after liver transplantation

作　　者：赖威[1] 卢实春[1] 王孟龙[1] 张静[1] 武聚山[1] 戴军[1] 曾道炳[1] 夏仁品[1] 李宁[1] 

机构地区：[1]首都医科大学附属北京佑安医院肝胆外科暨肝移植中心,100069

出　　处：《中华医学杂志》2009年第22期1529-1532,共4页National Medical Journal of China

基　　金：国家自然科学基金（30671977）;首都医学发展科研基金（2005-2034）

摘　　要：目的为了了解肝移植术后，基于钙调磷酸酶抑制剂（CNI）减量的吗替麦考酚酯（MMF）免疫抑制方案改善肝移植术后肾损害的临床效果。方法我们回顾分析3年内资料完整的124例肝移受体术后CNI相关肾损害发生情况，总结基于CNI减量的MMF免疫抑制方案改善肝移植术后肾损害的临床效果。结果124例肝移植受体中，有14例（11．29％）发生CNI相关肾损害，其中5例（5／22）发生于环孢素A（CsA）组，9例（9／102）发生于他克莫司（TAC）组，术后发生肾损害的时间为（12．92±9．04）个月（1—31个月）。TAC剂量降低约55％[（2．6±1．14）mg／d与（1．1±0．22）mg／d；t=3．000，P=0．040]，CsA剂量降低约70％（370±179）mg／d与（105±27）；t=3．359，P=0．028，MMF平均剂量为（1．05±0．15）g／d（0．5—1．5g／d）。免疫抑制方案调整后平均随访时间（6．00±3．37）个月（3—14个月），14例肾损害受体血清肌酐从（139±46）μmol／L降到第1、2、3个月的（122±46）μmol／L（t=3．152，P=0．004）、（114±53）μmol／L（t=4．180，P=0．001）和（93±18）μmol／L（t=4．721，P=0．000）；肌酐清除率从（52±21）ml／min增加到第1、2、3个月的（63±22）ml／min（t=-3．439．P=0．004）、（69±25）m]／min（t=-4．207，P=0．001）和（79±25）m]／min（t=-6．149，P=0．000）。71．43％（10／14）CNI相关肾损害受体血清肌酐水平恢复正常，21．43％（3／14）血清肌酐水平显著降低，7．14％（1／14）死于肾功能衰竭。结论基于CNI减量的MMF免疫抑制方案能持续显著改善肝移植术后CNI相关肾损害，并具有良好的安全性和耐受性。Objective Renal dysfunction caused by calcineurin inhibitor （CNI） after liver transplantation is a major complication among the long-term surviving recipients. Several studies have demonstrated that the adverse events could be prevented or avoided by mycophenolate mofetil （MMF）-based CNI reduced immunosuppressive protocol. In this retrospective study, we analyzed the middle-term effect of this regimen upon improving the CNI-associated renal dysfunction. Methods 124 OLT recipients＇ data within the recent three years were reviewed in this study. Results Renal dysfunction developed in 14 cases and its incidence was 11.29%. Five cases of them were from cyclosporine A （CsA） group and 9 from tacrolimus （TAC） group. The postoperative time ranged from 3-39 months with a mean follow-up duration of 19.26 ±9.30 months. The interval between renal impairment and surgery was 12.92 ± 9.04 （ 1 - 31 ） months. CNI were reduced stepwise by about 55% in TAC group （TAC 2.60 ± 1.14 mg/d vs 1.10 ±0. 22 mg/d ; t = 3. 000, P = 0.040） and about 70% in CsA group （ CsA 370 ± 179 mg/d vs 105± 27 ; t = 3. 359, P = 0. 028）. Serum creatinine had decreased from 139 ± 46 μmol/L to 122 ± 46μmol/L （ t = 3. 152, P = 0.004）, 114 ±53 μmol/L （t =4. 180, P =0. 001 ） and 93 ± 18 μmoL/L （t =4. 721, P =0. 000） after administrating a mean MMF dose of 1.05 ±0.15 g/d （0.5 - 1.5 g/d） for 1, 2 and 3 months respectively. And the creatinine clearance rate increased from 51.83 ± 21.28 ml/min to 63±22 ml/min （ t = - 3. 439, P = 0.004）, 69 ± 25 ml/min （t = - 4. 207, P = 0.001 ） and 79 ± 25 ml/min （ t = - 6. 149, P = 0. 000） during the corresponding period. Improvement was maintained within a follow-up period of 6.00± 3.37 （ 3 - 14） months without major immunological or non-immunological side effects, except for 1 recipient from another institution who died of CNI-associated renal failure within 1 month after burst. 71.43% （10/14） of recipients achieved the normalization of serum cr

关 键 词：肝脏移植 磷酸二脂水解酶抑制剂 吗替麦考酚酯 肾功能障碍 

分 类 号：R657.3[医药卫生—外科学] R699.2[医药卫生—临床医学]