• 1.四川大學(xué)華西醫(yī)院泌尿外科,成都610041 2.四川大學(xué)華西醫(yī)院中國循證醫(yī)學(xué)中心;

目的　 評價雷帕霉素為基礎(chǔ)免疫抑制劑治療中CsA保留與撤除近期與遠(yuǎn)期有效性和安全性.方法采用Cochrane系統(tǒng)評價
方法 　計算機(jī)檢索MEDLINE、EMBASE、Cochrane圖書館臨床對照試驗數(shù)據(jù)庫(CENTRAL)、CNKI等數(shù)據(jù)庫,檢索時間從1995年1月至2005年12月.納入以雷帕霉素為基礎(chǔ)免疫抑制劑治療中CsA保留與撤除近期與遠(yuǎn)期有效性和安全性的隨機(jī)對照試驗.由2名評價者共同評價納入研究的質(zhì)量,對同質(zhì)研究采用RevMan 4.2.7軟件進(jìn)行Meta分析.
結(jié)果 　共納入10個研究,腎移植術(shù)后患者1 121例.納入研究根據(jù)隨機(jī)方法、分配隱藏和盲法描述評分,6個為A級,4個為B級.Meta分析結(jié)果顯示,CsA撤除對患者生存率的OR(95%CI)值在6、12、24、36個月的分別為0.77(0.17, 3.52)、1.24(0.48, 3.16)、1.32(0.57, 3.08)、1.21(0.60, 2.41);移植腎存活率的OR(95%CI)值在6、12、24、36、48、54個月時分別為1.79(0.63, 5.06)、1.15(0.56, 2.36)、1.39(0.68, 2.85)、1.80(0.99, 3.29)、2.13(1.16, 3.89)、2.01(1.15, 3.51);急性排除反應(yīng)在6、12、24、36、48個月的OR(95%CI)值分別為0.92(0.48, 1.78)、1.90(1.25, 2.89)、2.01(0.94, 4.27)、1.93(0.93, 4.00)、1.52(0.77, 3.02).
結(jié)論 　現(xiàn)有研究結(jié)果顯示,腎移植術(shù)后病情穩(wěn)定患者,以雷帕霉素為基礎(chǔ)的免疫抑制劑治療中,CsA撤除在第1年易導(dǎo)致急性排斥反應(yīng)發(fā)生,但是對于人長期生存率無影響,同時有助于移植腎長期存活、腎功能恢復(fù).由于納入研究存在選擇性偏倚和測量性偏倚的高度可能性,勢必影響結(jié)果的證據(jù)強(qiáng)度,期待高質(zhì)量的隨機(jī)雙盲對照試驗提供高質(zhì)量的證據(jù).

引用本文： 張雁鋼,滕東海,王 莉,熊 瑋,白安勝,吳泰相,盧一平. 腎移植術(shù)后雷帕霉素為基礎(chǔ)的免疫抑制劑治療中環(huán)孢素A保留和撤除的近期及遠(yuǎn)期有效性和安全性評價. 中國循證醫(yī)學(xué)雜志, 2006, 06(2): 94-106. doi: 復(fù)制

1. 葉平.主編.血脂的基礎(chǔ)與臨床.第1版北京:人民軍醫(yī)出版社; 2002.205.
2. Renal Data System.USRDS 1998 annual data report.Bethesda,Md:National Institute of Diabetes and Digestive Kidney Disease,April 1998:39.(NIH publication no.98-3176).
3. Merion RM,White DJ,Thiru S,et al.Cyclosporine:five years’ experience in cadaveric renal transplantation.N Engl J Med JT-The New England Journal of Medicine,1984; 310(3):148-154.
4. Thiel G,Bock A,Spondlin M,et al.Long-term benefits and risks of cyclosporin A (sandimmun)-an analysis at 10 years.Transplantation Proceedings,1994; 26(5):2493-2498.
5. Sehgal SN,Baker H,Vezina C.Rapamycin (AY-22,989),a new antifungal antibiotic.Ⅱ.Fermentation,isolation and characterization.Journal of Antibiotics,1975; 28(10):727-732.
6. Kuypers DR.Benefit-risk assessment of sirolimus in renal transplantation.Drug Saf,2005; 28:153-181.
7. Stallone G,Di Paolo S,Schena A,et al.Early withdrawal of cyclosporine A improves 1-year kidney graft structure and function in sirolimus-treated patients.Transplantation,2003; 75(7):998-1003.
8. Kreis H,Oberbauer R,Campistol JM,et al.Long-term benefits with sirolimus-based therapy after early cyclosporine withdrawal.J Am Soc Nephrol,2004; 15(3):809-817.
9. Oberbauer R,Kreis H,Johnson RW,et al.Long-term improvement in renal function with sirolimus after early cyclosporine withdrawal in renal transplant recipients:2-year results of the Rapamune Maintenance Regimen Study.Transplantation,2003; 76(2):364-370.
10. Legendre C,Campistol JM,Squifflet JP,et al.Cardiovascular risk factors of sirolimus compared with cyclosporine:early experience from two randomized trials in renal transplantation.Transplantation Proceedings,2003; 35(3 Suppl):151S-153S.
11. Gonwa TA,Hricik DE,Brinker K,et al.Improved renal function in sirolimus-treated renal transplant patients after early cyclosporine elimination.Transplantation,2002; 74(11):1560-1567.
12. Mathew T,Kreis H,Friend P.Two-year incidence of malignancy in sirolimus-treated renal transplant recipients:Results from five multicenter studies.Clinical Transplantation,2004; 18(4):446-449.
13. Baboolal K.A phase Ⅲ prospective,randomized study to evaluate concentration-controlled sirolimus (rapamune) with cyclosporine dose minimization or elimination at six months in de novo renal allograft recipients.Transplantation,2003; 75(8):1404-1408.
14. Campistol TM,Kreis H,Oberbauer R,et al.Sirolimus-based therapy following early cyclosporine withdrawal resulted in superior renal allograft survival at 48 months compared with continuous combined sirolimus and cyclosporine.American Journal of Transplantation,2004; (4):S8:344.
15. Johnson RW,Kreis H,Oberbauer R,et al.Sirolimus allows early cyclosporine withdrawal in renal transplantation resulting in improved renal function and lower blood pressure.Transplantation,2001; 72(5):777-786.
16. Jardine AG.Phase Ⅲ prospective,randomized study to evaluate the safety and efficacy of concentration controlled rapamune (sirolimus) with ciclosporin dose minimisation or elimination in de novo renal allograft recipients at 12 months.American Journal of Transplantation,2004; 260(Suppl 8):286.
17. Pascual M,Theruvath T,Kawai T,et al.Strategies to improve long-term outcomes after renal transplantation.N Engl J Med,2002; 346(8):580-590.
18. Bakker RC,Hollander AA,Mallat MJ,et al.Conversion from cyclosporine to azathioprine at three months reduces the incidence of chronic allograft nephropathy.Kidney Int,2003; 64(3):1027-1034.
19. Gallagher MP,Hall B,Craig J,et al.A randomized controlled trial of cyclosporine withdrawal in renal-transplant recipients:15-year results.Transplantation,2004; 78(11):1653-1660.
20. Oliveira JG,Xavier P,Sampaio SM,et al.Compared to mycophenolate mofetil,rapamycin induces significant changes on growth factors and growth factor receptors in the early days post-kidney transplantation.Transplantation,2002; 73(6):915-920.
21. Ye P.Editor-in-Chief.Basic and Clinical Research of Bood Fat.1st Edition.Beijing:The People’s Medicine Press; 2002.205.
22. Hong JC,Kahan BD.Sirolimus-induced thrombocytopenia and leukopenia in renal transplant recipients:risk factors,incidence,progression,and management.Transplantation,2000; 69(10):2085-2090.
23. van der Vliet JA,Barendregt WB,Hoitsma AJ,et al.Increased incidence of renal allograft thrombosis after continuous ambulatory peritoneal dialysis.Clin Transplant,1996; 10(1):51-54.
24. Singh A,Stablein D,Tejani A.Risk factors for vascular thrombosis in pediatric renal transplantation:a special report of the North American Pediatric Renal Transplant Cooperative Study.Transplantation,1997; 63(9):1263-1267.
25. Wagenknecht DR,Fastenau DR,Torry RJ,et al.Antiphospholipid antibodies are a risk factor for early renal allograft failure:isolation of antiphospholipid antibodies from a thrombosed renal allograft.Transplant Proc,1999; 31(1-2):285-288.
26. Guo CM.Spontaneity arterial thrombus in children.Foreign Med Sci,1999; 26:331.
  1. 1. 葉平.主編.血脂的基礎(chǔ)與臨床.第1版北京:人民軍醫(yī)出版社; 2002.205.
  2. 2. Renal Data System.USRDS 1998 annual data report.Bethesda,Md:National Institute of Diabetes and Digestive Kidney Disease,April 1998:39.(NIH publication no.98-3176).
  3. 3. Merion RM,White DJ,Thiru S,et al.Cyclosporine:five years’ experience in cadaveric renal transplantation.N Engl J Med JT-The New England Journal of Medicine,1984; 310(3):148-154.
  4. 4. Thiel G,Bock A,Spondlin M,et al.Long-term benefits and risks of cyclosporin A (sandimmun)-an analysis at 10 years.Transplantation Proceedings,1994; 26(5):2493-2498.
  5. 5. Sehgal SN,Baker H,Vezina C.Rapamycin (AY-22,989),a new antifungal antibiotic.Ⅱ.Fermentation,isolation and characterization.Journal of Antibiotics,1975; 28(10):727-732.
  6. 6. Kuypers DR.Benefit-risk assessment of sirolimus in renal transplantation.Drug Saf,2005; 28:153-181.
  7. 7. Stallone G,Di Paolo S,Schena A,et al.Early withdrawal of cyclosporine A improves 1-year kidney graft structure and function in sirolimus-treated patients.Transplantation,2003; 75(7):998-1003.
  8. 8. Kreis H,Oberbauer R,Campistol JM,et al.Long-term benefits with sirolimus-based therapy after early cyclosporine withdrawal.J Am Soc Nephrol,2004; 15(3):809-817.
  9. 9. Oberbauer R,Kreis H,Johnson RW,et al.Long-term improvement in renal function with sirolimus after early cyclosporine withdrawal in renal transplant recipients:2-year results of the Rapamune Maintenance Regimen Study.Transplantation,2003; 76(2):364-370.
  10. 10. Legendre C,Campistol JM,Squifflet JP,et al.Cardiovascular risk factors of sirolimus compared with cyclosporine:early experience from two randomized trials in renal transplantation.Transplantation Proceedings,2003; 35(3 Suppl):151S-153S.
  11. 11. Gonwa TA,Hricik DE,Brinker K,et al.Improved renal function in sirolimus-treated renal transplant patients after early cyclosporine elimination.Transplantation,2002; 74(11):1560-1567.
  12. 12. Mathew T,Kreis H,Friend P.Two-year incidence of malignancy in sirolimus-treated renal transplant recipients:Results from five multicenter studies.Clinical Transplantation,2004; 18(4):446-449.
  13. 13. Baboolal K.A phase Ⅲ prospective,randomized study to evaluate concentration-controlled sirolimus (rapamune) with cyclosporine dose minimization or elimination at six months in de novo renal allograft recipients.Transplantation,2003; 75(8):1404-1408.
  14. 14. Campistol TM,Kreis H,Oberbauer R,et al.Sirolimus-based therapy following early cyclosporine withdrawal resulted in superior renal allograft survival at 48 months compared with continuous combined sirolimus and cyclosporine.American Journal of Transplantation,2004; (4):S8:344.
  15. 15. Johnson RW,Kreis H,Oberbauer R,et al.Sirolimus allows early cyclosporine withdrawal in renal transplantation resulting in improved renal function and lower blood pressure.Transplantation,2001; 72(5):777-786.
  16. 16. Jardine AG.Phase Ⅲ prospective,randomized study to evaluate the safety and efficacy of concentration controlled rapamune (sirolimus) with ciclosporin dose minimisation or elimination in de novo renal allograft recipients at 12 months.American Journal of Transplantation,2004; 260(Suppl 8):286.
  17. 17. Pascual M,Theruvath T,Kawai T,et al.Strategies to improve long-term outcomes after renal transplantation.N Engl J Med,2002; 346(8):580-590.
  18. 18. Bakker RC,Hollander AA,Mallat MJ,et al.Conversion from cyclosporine to azathioprine at three months reduces the incidence of chronic allograft nephropathy.Kidney Int,2003; 64(3):1027-1034.
  19. 19. Gallagher MP,Hall B,Craig J,et al.A randomized controlled trial of cyclosporine withdrawal in renal-transplant recipients:15-year results.Transplantation,2004; 78(11):1653-1660.
  20. 20. Oliveira JG,Xavier P,Sampaio SM,et al.Compared to mycophenolate mofetil,rapamycin induces significant changes on growth factors and growth factor receptors in the early days post-kidney transplantation.Transplantation,2002; 73(6):915-920.
  21. 21. Ye P.Editor-in-Chief.Basic and Clinical Research of Bood Fat.1st Edition.Beijing:The People’s Medicine Press; 2002.205.
  22. 22. Hong JC,Kahan BD.Sirolimus-induced thrombocytopenia and leukopenia in renal transplant recipients:risk factors,incidence,progression,and management.Transplantation,2000; 69(10):2085-2090.
  23. 23. van der Vliet JA,Barendregt WB,Hoitsma AJ,et al.Increased incidence of renal allograft thrombosis after continuous ambulatory peritoneal dialysis.Clin Transplant,1996; 10(1):51-54.
  24. 24. Singh A,Stablein D,Tejani A.Risk factors for vascular thrombosis in pediatric renal transplantation:a special report of the North American Pediatric Renal Transplant Cooperative Study.Transplantation,1997; 63(9):1263-1267.
  25. 25. Wagenknecht DR,Fastenau DR,Torry RJ,et al.Antiphospholipid antibodies are a risk factor for early renal allograft failure:isolation of antiphospholipid antibodies from a thrombosed renal allograft.Transplant Proc,1999; 31(1-2):285-288.
  26. 26. Guo CM.Spontaneity arterial thrombus in children.Foreign Med Sci,1999; 26:331.