腎移植術后應用驍悉與硫唑嘌呤的安全性評價_《中國循證醫學雜志》

作者：

1. 四川大學華西醫院泌尿外科,成都,6100412. 成都市第三人民醫院神經內科,成都,6100313. 四川大學華西醫院中國循證醫學中心4. 四川大學華西醫院衛生部移植工程與移植免疫重點實驗室;

關鍵詞：

驍悉硫唑嘌呤腎移植藥物不良反應系統評價

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目的　系統評價腎移植術后免疫抑制劑驍悉(mycophenolate mofetil,MMF)與硫唑嘌呤(azathioprine,AZA)導致的不良反應發生情況.
方法　計算機檢索MEDLINE(1966～2004.6)、EMBASE(1984～2004.6)、Cochrane圖書館(2004第2期)及中國生物醫學文獻數據庫(1979～2004.6),納入涉及腎移植術后使用MMF與AZA出現不良反應的隨機對照試驗(RCT),對其方法學質量進行評價后,采用RevMan 4.11軟件進行統計分析.
結果　共納入24個RCT,涉及不同劑量MMF與AZA治療腎移植術后的排斥反應.MMF的胃腸道不良反應發生率明顯高于AZA,特別是MMF3 g/d組的嘔吐、腹痛、腹瀉發生率與AZA組比較有明顯差異(P lt;0.05).MMF3 g/d組的巨細胞病毒感染發生率在6個月、1年及3年觀察期內明顯高于AZA組,其差異有統計學意義;MMF2 g/d組在1年隨訪期內感染發生率也高于AZA組.MMF3 g/d組的白細胞減少發生率明顯高于AZA組,其差異有統計學意義;而MMF2 g/d組的白細胞減少發生率與AZA組相比差異不具統計學意義.MMF的血小板減少發生率低于AZA組,MMF3 g/d組與AZA組相比差異有統計學意義.MMF各組及AZA組皮膚腫瘤的發生率無明顯差異.
結論　MMF與AZA相比,其不良反應發生主要表現為較高的胃腸道不良反應、白細胞減少發生率和機會感染發生率,較低的血小板減少發生率.而且不良反應的發生呈現一定的劑量效應關系.

引用本文： 王坤杰,張海濤,李幼平,盧一平,魏強,李虹,楊宇如. 腎移植術后應用驍悉與硫唑嘌呤的安全性評價. 中國循證醫學雜志, 2005, 05(5): 365-374. doi: 復制

1.	紀玉蓮, 楊彥強, 楊光寶, 余學清,姜宗培,沈清端,吳培根,朱蘭英. 霉酚酸酯預防腎移植術后急性排斥反應臨床觀察[J]. 中山醫科大學學報,2001; 22(3): 215-217.
2.	黃麗萍, 楊詩玉, 武小桐, 陳再彬, 王振興, 衛熹. 腎移植患者術后早期應用霉酚酸酯的臨床觀察[J]. 中華器官移植雜志, 2000; 21(5): 294-295.
3.	郭宏波, 張玉海. 霉酚酸酯(MMF)在腎移植中的應用[J]. 中國新藥雜志, 1998; 7(6): 444-446.
4.	凌建煜, 祝宇, 孫福康. 驍悉與小劑量環孢素A在尸體腎移植中的聯合應用[J]. 中華器官移植雜志, 1998; 19(3): 175-176.
5.	王慶文, 季曙明, 陳勁松, 殷立平, 徐斌, 陳惠萍, 黎磊石. 霉酚酸酯預防尸體腎移植急性排斥反應[J]. 腎臟病與透析腎移植雜志,1998; 7(1): 34-37.
6.	張海濤, 王坤杰, 李幼平, 高勵, 劉瑾, 蔡羽嘉. 腎移植術后驍悉與硫唑嘌呤抗排斥反應隨機對照試驗的系統評價 [J]. 中國循證醫學雜志, 2004; 4(2): 79-91.
7.	US Renal Transplant Mycophenolate Mofetil Study Group. Mycophenolate mofetil in cadaveric renal transplantation[J]. Am J Kidney Disease, 1999; 34(2): 296-303.
8.	Miller J, Mendez R, Pirsch JD, Jensik SC. Safety and efficacy of tacrolimus in combination with mycophenolate mofetil in cadaveric renal transplant recipients[J]. Transplantation, 2000; 69(5): 875-880.
9.	The Mycophenolate Mofetil Acute Renal Rejection Study Group. Mycophenolate mofetil for the treatment of a first acute renal allograft rejection: three-year follow-up[J]. Transplantation, 2001; 71(8): 1091-1097.
10.	Johnson C, Ahsan N, Gonwa T, Hallorax P, Stegall M, Hardy M, Metzger R, Shield C, Rocher L, Scandling J. Random trial of tacrolimus in combination with AZAthioprine or mycophenolate mofetil versus cyclosporine with mycophenolate mofetil after cadaveric kidney transplantation[J]. Transplantation, 2000; 69(5): 834-841.
11.	Jirasiritham S, Sumethkul V, Mavichak V, Chalermsanyakorn P. The treatment of chronic rejection with mycophenolate mofetil versus AZAthioprine in kidney transplantation[J]. Transplant Proc, 2000; 32(7): 2040-2042.
12.	Suhail SM, Vathsala A, Lou HX, Woo KT. Safety and efficacy of mycophenolate mofetil for prophylaxis in Asian renal transplant recipients[J]. Transplant Proc, 2000; 32(7):1757-1758.
13.	Mathew TH. A blinded, long-time, randomized multicenter study of mycophenolate mofetil in cadaveric renal transplantation: result at three years[J]. Transplantation, 1998; 65(11): 1450-1454.
14.	Mendez R. FK506 and mycophenolate mofetil in renal transplant recipients: six-month result of a multicenter, randomized dose ranging trial[J]. Transplantation Proc, 1998; 30(4):1287-1289.
15.	The Mycophenolate mofetil Acute Renal Rejection Study Group. Mycophenolate mofetil for the treatment of a first acute renal allograft rejection[J]. Transplantation, 1998; 65(2): 235-241.
16.	Neylan JE. Immunosupppressive therapy in high-risk transplant patients: dose-dependent efficacy of mycophenolate mofetil in African-American renal allograft recipients[J]. Transplantation, 1997; 64(9): 1277-1282.
17.	The U.S. Mycophenolate Mofetil Study Group. Mycophenolate mofetil for the prevention of acute rejection of primary cadaveric kidney transplants: status of the MYC 1866 study at 1 year[J]. Transplant Proc, 1997; 29(1-2): 348-349.
18.	The Tricontinental Mycophnolate Mofetil Rneal Transplantation Study Group. A blinded, randomized clinical trial of mycophenolate mofetil for the prevention of acute rejection in cadaveric renal transplantation[J]. Transplantation, 1996; 61(7): 1029-1037.
19.	European Mycophenolate Mofetil Cooperative Study Group. Mycophenolate in renal transplantation: 3-year results from the placebo-controlled trial[J]. Transplantation, 1999; 68(3): 391-396.
20.	Solinger HW. Mycophenolate mofetil for the prevention of acute rejection in primary cadaveric renal allograft recipients[J]. Transplantation, 1995; 60(3): 225-232.
21.	European Mycophenolate Mofetil Cooperative Study Group. Placebo-controlled study of mycophenolate mofetil combined with cyclosporin and corticosteroid for prevention of acute rejection[J]. Lancet, 1995; 345(8 961): 1321-1325.
22.	Ji YL, Yang YQ, Yang GB, Yu XQ, Jiang PZ, Shen QD, Wu PG, Zhu LY. The clinical investigation of mycophenolate mofetil for the prevention of acute rejection[J]. Acad J SUMS, 2001; 22(3): 215-217.
23.	Huang LP, Yang SY, Wu XT, Chen ZB, Wang ZX, Wei X. Clinical observation on the early application of cellcept following cadaveric renal tansplantation[J]. Chin J Organ Transplant, 2000; 21(5): 294-295.
24.	Guo HB, Zhang YH. The use of mycophenolate mofetil in renal tansplantation[J]. China J New Drug, 1998; 7(6): 444-446.
25.	Ling JY, Zhu Y, Sun FK. Combined use of MMF with low dosage of cyclosporine A in renal tansplantation[J]. Chin J Organ Transplant, 1998; 19(3): 175-176.
26.	Wang QW, Ji SM, Chen JS, Yin LP, Xu B, Chen HP, Li LS. Prevention acute rejection of MMF in renal transplantation[J]. J Nephrol Dialy Transplant, 1998; 7(1): 34-37.
27.	Giuseppe R, Mariadomenica L, Eliana G, Maria G, Borislav DD, Bogdan EI, Giulia G, Donato D, Maurizio S, Silvio S, Umberto V, Giuseppe S, Georges M, Stefano F, Paolo R, Vito S, Jean-Louis B, Norberto P, Piero R. Mycophenolate mofetil versus AZAthioprine for prevention of acute rejection in renal transplantation (MYSS): a randomised trial[J]. Lancet, 2004; 364(7): 503-512.
28.	Sami S, Jos′e M, Manuel A, Jacques S, Jean-paul S, Bruno V, Short-term combination of mcophenolate mofetil with cyclosporine as a therapeutic option for renal transplant recipients[J]. Transplantation, 2002; 74(4): 511-517.
29.	Miladipour AH, Ghods AJ, Nejadgashti H. Effect of mcophenolate mofetil on the prevention of acute renal allograft rejection[J]. Transplantation Proceedings, 2002; 34: 2089-2090.
30.	Metcalfe MS, Jain S, Waller JR, Saunders RN, Bicknell GR, Nicholson ML. A randomized trial of mycophenolate mofetil versus AZAthioprine as calcineurin inhibitor sparing agents in the treatment of chronic allograft nephropathy[J]. Transplantation Proceedings, 2002; 34:1812-1814.
31.	Zhang HT, Wang KJ, Li YP, Gao L, Liu J, Cai YJ. Systematic review of clinical research literatures about comparison mycophenolate acid and AZAthioprine after renal transplantation[J]. Chin J of EBM, 2004; 4(2): 79-91.
32.	Halloran P, Mathew T, Tomlanovich S, Groth C, Hooftman L, Barker C. Mycophenolate mofetil in renal allograft recipients: a pooled efficacy analysis of three randomized, double-blind, clinical studies in prevention of rejection[J]. Transplantation, 1997; 63(1): 39-47.
33.	Warrens AN. The evolving role of mycophenolate mofetil in renal transplantation[J]. Q J Med, 2000; 93(3): 15-20.
34.	Smak Gregoor PJ, Hesse CJ, van Gelder T. Relation of mycophenolic acid trough levels and adverse events in kidney allograft recipients[J]. Transplant Proc, 1998; 30(423): 1192-1193.
35.	Van Gelder T, Hilbrands LB, Vanrenterghem Y. A randomized double-blind, multicenter plasma concentration controlled study of the safety and efficacy of oral mycophenolate mofetil for the prevention of acute rejection after kidney transplantation[J]. Transplantation, 1999; 68(563): 261-266.
36.	Shaw LM, Sollinger HW, Halloran P. Mycophenolate mofetil: a report of the consensus panel[J]. Ther Drug Monit, 1995; 17(43): 690-699.
37.	Pillans PI, Rigby RJ, Kubler P. A retrospective analysis of mycophenolic acid and cyclosporin concentrations with acute rejection in renal transplant recipients[J]. Clin Biochem, 2001; 34(43):77-81.

1. 紀玉蓮, 楊彥強, 楊光寶, 余學清,姜宗培,沈清端,吳培根,朱蘭英. 霉酚酸酯預防腎移植術后急性排斥反應臨床觀察[J]. 中山醫科大學學報,2001; 22(3): 215-217.
2. 黃麗萍, 楊詩玉, 武小桐, 陳再彬, 王振興, 衛熹. 腎移植患者術后早期應用霉酚酸酯的臨床觀察[J]. 中華器官移植雜志, 2000; 21(5): 294-295.
3. 郭宏波, 張玉海. 霉酚酸酯(MMF)在腎移植中的應用[J]. 中國新藥雜志, 1998; 7(6): 444-446.
4. 凌建煜, 祝宇, 孫福康. 驍悉與小劑量環孢素A在尸體腎移植中的聯合應用[J]. 中華器官移植雜志, 1998; 19(3): 175-176.
5. 王慶文, 季曙明, 陳勁松, 殷立平, 徐斌, 陳惠萍, 黎磊石. 霉酚酸酯預防尸體腎移植急性排斥反應[J]. 腎臟病與透析腎移植雜志,1998; 7(1): 34-37.
6. 張海濤, 王坤杰, 李幼平, 高勵, 劉瑾, 蔡羽嘉. 腎移植術后驍悉與硫唑嘌呤抗排斥反應隨機對照試驗的系統評價 [J]. 中國循證醫學雜志, 2004; 4(2): 79-91.
7. US Renal Transplant Mycophenolate Mofetil Study Group. Mycophenolate mofetil in cadaveric renal transplantation[J]. Am J Kidney Disease, 1999; 34(2): 296-303.
8. Miller J, Mendez R, Pirsch JD, Jensik SC. Safety and efficacy of tacrolimus in combination with mycophenolate mofetil in cadaveric renal transplant recipients[J]. Transplantation, 2000; 69(5): 875-880.
9. The Mycophenolate Mofetil Acute Renal Rejection Study Group. Mycophenolate mofetil for the treatment of a first acute renal allograft rejection: three-year follow-up[J]. Transplantation, 2001; 71(8): 1091-1097.
10. Johnson C, Ahsan N, Gonwa T, Hallorax P, Stegall M, Hardy M, Metzger R, Shield C, Rocher L, Scandling J. Random trial of tacrolimus in combination with AZAthioprine or mycophenolate mofetil versus cyclosporine with mycophenolate mofetil after cadaveric kidney transplantation[J]. Transplantation, 2000; 69(5): 834-841.
11. Jirasiritham S, Sumethkul V, Mavichak V, Chalermsanyakorn P. The treatment of chronic rejection with mycophenolate mofetil versus AZAthioprine in kidney transplantation[J]. Transplant Proc, 2000; 32(7): 2040-2042.
12. Suhail SM, Vathsala A, Lou HX, Woo KT. Safety and efficacy of mycophenolate mofetil for prophylaxis in Asian renal transplant recipients[J]. Transplant Proc, 2000; 32(7):1757-1758.
13. Mathew TH. A blinded, long-time, randomized multicenter study of mycophenolate mofetil in cadaveric renal transplantation: result at three years[J]. Transplantation, 1998; 65(11): 1450-1454.
14. Mendez R. FK506 and mycophenolate mofetil in renal transplant recipients: six-month result of a multicenter, randomized dose ranging trial[J]. Transplantation Proc, 1998; 30(4):1287-1289.
15. The Mycophenolate mofetil Acute Renal Rejection Study Group. Mycophenolate mofetil for the treatment of a first acute renal allograft rejection[J]. Transplantation, 1998; 65(2): 235-241.
16. Neylan JE. Immunosupppressive therapy in high-risk transplant patients: dose-dependent efficacy of mycophenolate mofetil in African-American renal allograft recipients[J]. Transplantation, 1997; 64(9): 1277-1282.
17. The U.S. Mycophenolate Mofetil Study Group. Mycophenolate mofetil for the prevention of acute rejection of primary cadaveric kidney transplants: status of the MYC 1866 study at 1 year[J]. Transplant Proc, 1997; 29(1-2): 348-349.
18. The Tricontinental Mycophnolate Mofetil Rneal Transplantation Study Group. A blinded, randomized clinical trial of mycophenolate mofetil for the prevention of acute rejection in cadaveric renal transplantation[J]. Transplantation, 1996; 61(7): 1029-1037.
19. European Mycophenolate Mofetil Cooperative Study Group. Mycophenolate in renal transplantation: 3-year results from the placebo-controlled trial[J]. Transplantation, 1999; 68(3): 391-396.
20. Solinger HW. Mycophenolate mofetil for the prevention of acute rejection in primary cadaveric renal allograft recipients[J]. Transplantation, 1995; 60(3): 225-232.
21. European Mycophenolate Mofetil Cooperative Study Group. Placebo-controlled study of mycophenolate mofetil combined with cyclosporin and corticosteroid for prevention of acute rejection[J]. Lancet, 1995; 345(8 961): 1321-1325.
22. Ji YL, Yang YQ, Yang GB, Yu XQ, Jiang PZ, Shen QD, Wu PG, Zhu LY. The clinical investigation of mycophenolate mofetil for the prevention of acute rejection[J]. Acad J SUMS, 2001; 22(3): 215-217.
23. Huang LP, Yang SY, Wu XT, Chen ZB, Wang ZX, Wei X. Clinical observation on the early application of cellcept following cadaveric renal tansplantation[J]. Chin J Organ Transplant, 2000; 21(5): 294-295.
24. Guo HB, Zhang YH. The use of mycophenolate mofetil in renal tansplantation[J]. China J New Drug, 1998; 7(6): 444-446.
25. Ling JY, Zhu Y, Sun FK. Combined use of MMF with low dosage of cyclosporine A in renal tansplantation[J]. Chin J Organ Transplant, 1998; 19(3): 175-176.
26. Wang QW, Ji SM, Chen JS, Yin LP, Xu B, Chen HP, Li LS. Prevention acute rejection of MMF in renal transplantation[J]. J Nephrol Dialy Transplant, 1998; 7(1): 34-37.
27. Giuseppe R, Mariadomenica L, Eliana G, Maria G, Borislav DD, Bogdan EI, Giulia G, Donato D, Maurizio S, Silvio S, Umberto V, Giuseppe S, Georges M, Stefano F, Paolo R, Vito S, Jean-Louis B, Norberto P, Piero R. Mycophenolate mofetil versus AZAthioprine for prevention of acute rejection in renal transplantation (MYSS): a randomised trial[J]. Lancet, 2004; 364(7): 503-512.
28. Sami S, Jos′e M, Manuel A, Jacques S, Jean-paul S, Bruno V, Short-term combination of mcophenolate mofetil with cyclosporine as a therapeutic option for renal transplant recipients[J]. Transplantation, 2002; 74(4): 511-517.
29. Miladipour AH, Ghods AJ, Nejadgashti H. Effect of mcophenolate mofetil on the prevention of acute renal allograft rejection[J]. Transplantation Proceedings, 2002; 34: 2089-2090.
30. Metcalfe MS, Jain S, Waller JR, Saunders RN, Bicknell GR, Nicholson ML. A randomized trial of mycophenolate mofetil versus AZAthioprine as calcineurin inhibitor sparing agents in the treatment of chronic allograft nephropathy[J]. Transplantation Proceedings, 2002; 34:1812-1814.
31. Zhang HT, Wang KJ, Li YP, Gao L, Liu J, Cai YJ. Systematic review of clinical research literatures about comparison mycophenolate acid and AZAthioprine after renal transplantation[J]. Chin J of EBM, 2004; 4(2): 79-91.
32. Halloran P, Mathew T, Tomlanovich S, Groth C, Hooftman L, Barker C. Mycophenolate mofetil in renal allograft recipients: a pooled efficacy analysis of three randomized, double-blind, clinical studies in prevention of rejection[J]. Transplantation, 1997; 63(1): 39-47.
33. Warrens AN. The evolving role of mycophenolate mofetil in renal transplantation[J]. Q J Med, 2000; 93(3): 15-20.
34. Smak Gregoor PJ, Hesse CJ, van Gelder T. Relation of mycophenolic acid trough levels and adverse events in kidney allograft recipients[J]. Transplant Proc, 1998; 30(423): 1192-1193.
35. Van Gelder T, Hilbrands LB, Vanrenterghem Y. A randomized double-blind, multicenter plasma concentration controlled study of the safety and efficacy of oral mycophenolate mofetil for the prevention of acute rejection after kidney transplantation[J]. Transplantation, 1999; 68(563): 261-266.
36. Shaw LM, Sollinger HW, Halloran P. Mycophenolate mofetil: a report of the consensus panel[J]. Ther Drug Monit, 1995; 17(43): 690-699.
37. Pillans PI, Rigby RJ, Kubler P. A retrospective analysis of mycophenolic acid and cyclosporin concentrations with acute rejection in renal transplant recipients[J]. Clin Biochem, 2001; 34(43):77-81.

《中國循證醫學雜志》

腎移植術后應用驍悉與硫唑嘌呤的安全性評價

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《中國循證醫學雜志》

腎移植術后應用驍悉與硫唑嘌呤的安全性評價

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

Format

Content

摘要全文圖表視頻參考文獻施引文獻補充材料