• 四川大學(xué)華西醫(yī)院腎臟內(nèi)科（成都，610041）;

新型免疫抑制劑的使用使移植腎的存活率明顯增加，但機(jī)會(huì)性感染的發(fā)生也隨之增多。巨細(xì)胞病毒（CMV）感染是腎移植術(shù)后常見(jiàn)的并發(fā)癥，除可引起直接損害外，還可對(duì)機(jī)體產(chǎn)生間接影響。現(xiàn)就腎移植術(shù)后巨細(xì)胞病毒感染的途徑、危險(xiǎn)因素、臨床表現(xiàn)、實(shí)驗(yàn)室檢查及防治進(jìn)展作一綜述。

引用本文： 于笑笑,柳飛,陶冶. 腎移植術(shù)后巨細(xì)胞病毒感染研究進(jìn)展. 華西醫(yī)學(xué), 2012, 27(4): 630-633. doi: 復(fù)制

1. 　Humar A, Snydman D, AST Infectious Diseases Community of Practice. Cytomegalovirus in solid organ transplant recipients[J]. Am J Transplant，2009，9 (4): 78-86.
2. 　De Keyzer K, Van Laecke S, Peeters P, et al. Human cytomegalovirus and kidney transplantation: a clinician’s update[J]. Am J Kidney Dis, 2011, 58(1): 118-126.
3. 　Hu JH, Zhao H, Huang YP, et al. Opportunistic posttransplantation virus infections in renal transplant recipients[J]. Transplant Proc, 2011, 43(10): 3715-3719.
4. 　Fortun J, Martin-Davila P, Pascual J, et al. Immunosuppressive therapy and infection after kidney transplantation[J]. Transpl Infect Dis, 2010, 12(5): 397-405.
5. 　Tian JH, Wang X, Yang KH, et al. Induction with and without antithymocyte globulin combined with cyclosporine/tacrolimus-based immunosuppression in renal transplantation: a meta-analysis of randomized controlled trials[J]. Transplant Proc, 2009 , 41(9): 3671-3676.
6. 　Prichard MN, Kern ER. The search for new therapies for human cytomegalovirus infections[J]. Virus Res, 2011, 157(2): 212-221.
7. 　魏強(qiáng), 于立新, 鄧文鋒, 等. 腎移植術(shù)后感染巨細(xì)胞病毒性肺炎的多因素分析[J]. 南方醫(yī)科大學(xué)學(xué)報(bào), 2009, 29(6): 1182-1184.
8. 　Crough T, Khanna R. Immunobiology of human cytomegalovi-rus: from bench to bedside[J]. Clin Microbiol Rev, 2009, 2(1): 76-98.
9. 　Razonable RR, Paya CV. Herpesvirus infections in transplant recipients: current challenges in the clinical management of cytomegalovirus and epstein-barr virus infections[J]. Herpes, 2003, 10(3): 60-65.
10. 　滕東海, 田靜. 巨細(xì)胞病毒感染與腎移植[J]. 華西醫(yī)學(xué), 2003, 3(2): 411-412.
11. 　Dzabic M, Rahbar A, Yaiw KC, et al. Intragraft cytomegalovirus protein expression is associated with reduced renal allograft survival[J]. Clin Infect Dis, 2011, 53(10): 969-976.
12. 　Helanterä I, Loqinov R, Koskinen P, et al. Persistent cytomegalovirus infection is associated with increased expression of TGF-b 1, PDGF-AA and ICAM-1 and arterial intimal thickening in kidney allografts[J]. Nephrol Dial Transplant, 2005, 20(4): 790-796.
13. 　Reischiq T, Jindra P, Hes O, et al. Effect of cytomegalovirus viremia on subclinical rejection or interstitial fibrosis and tubular atrophy in protocol biopsy at 3 months in renal allograft recipients managed by preemptive therapy or antiviral prophylaxis[J]. Transplantation, 2009, 87(3): 436-444.
14. 　Hjelmesæth J, Sagedal S, Hartmann A, et al. Asymptomatic cytomegalovirus infection is associated with increased risk of new-onset diabetes mellitus and impaired insulin release after renal transplantation[J]. Diabetologia, 2004, 47(9): 1550-1556.
15. 　De Keyzer K, Van Laecke S, Peeters P, et al. Denovo thrombotic microangiopathy induced by cytomegalovirus infection leading to renal allograft loss[J]. Am J Nephrol, 2010, 32(5): 491-496.
16. 　Sagedal S, Hartmann A, Nordal KP, et al. Impact of early cytomegalovirus infection and disease on long-term recipient and kidney graft survival[J]. Kidney Int, 2004, 66(1): 329-337.
17. 　Kalis RS, Hudson SL, Gaston RS. Determinants of Cardiovascular Mortality After Renal Transplantation: A Role For Cytomegalovirus?[J]. Am J Transplant, 2003, 3(1): 79-81.
18. 　Kim CK, Song JH, Kim SM, et al. Clinical usefulness of human cytomegalovirus antigenemia assay after kidney transplantation[J]. Transplantation, 2003, 75(12): 2151-2155.
19. 　范文勇. 實(shí)時(shí)熒光定量-PCR和酶聯(lián)免疫吸附法檢測(cè)巨細(xì)胞病毒-IgM抗體的比較[J]. 醫(yī)學(xué)檢驗(yàn), 2011, 8(2): 83-85.
20. 　Rhee JY, Peck KR, Lee NY, et al. Clinical usefulness of plasma quantitative polymerase chain reaction assay: diagnosis of cytomegalovirus infection in kidney transplant recipients[J]. Transplant Proc, 2011, 43(7): 2624-2629.
21. 　Kotton CN, Kumar D, Caliendo AM, et al. International consensus guidelines on the management of cytomegalovirus in solid organ transplantation[J]. Transplantation, 2010, 89(7): 779-795.
22. 　Winston DJ, Young JA, Pullarkat V, et al. Maribavir prophylaxis for prevention of cytomegalovirus infection in allogeneic stem-cell transplant recipients: a multicenter, randomized, double-blind,placebo-controlled, dose-ranging study[J]. Blood, 2008, 111(11): 5403-5410.
23. 　Hodson EM, Jones CA, Webster AC, et al. Antiviral medications to prevent cytomegalovirus disease and early death in recipients of solid-organ transplants: a systematic review of randomized con-trolled trials[J]. Lancet, 2005, 365: 2105-2115.
24. 　Johnson RJ, Clatworthy MR, Brich R, et al. CMV mismatch does not affect patient and graft survival in UK renal transplant recipients[J]. Transplantation, 2009, 88(1): 77-82.
25. 　Chamberlain CE, Penzak SR, Alfaro RM, et al. Pharmacokinetics of low and maintenance dose valganciclovir in kidney transplant recipients[J]. Am J Transplant, 2008, 8(6): 1297-1302.
26. 　Humar A, Lebranchu Y, Vincenti F, et al. The efficacy and safety of 200 days valganciclovir cytomegalovirus prophylaxis in high-risk kidney transplant recipients[J]. Am J Transplant, 2010, 10(5): 1228-1237.
27. 　Humar A, Limaye AP, Blumberq EA, et al. Extended valganciclovir prophylaxis in D+/R- kidney transplant recipients is associated with long-term reduction in cytomegalovirus disease: two-year results of the IMPACT study[J]. Transplantation, 2010, 90(12): 1427-1431.
28. 　San Juan R, Yebra M, Lumbreras C, et al. A new strategy of delayed long-term prophylaxis could prevent cytomegalovirus disease in (D+/R-) solid organ transplant recipients[J]. Clin Transplant, 2009, 23(5): 666-671.
29. 　Boillat Blanc N, Pascual M, Venetz JP, et al. Impact of a preemptive strategy after 3 months of valganciclovir cytomegalovirus prophylaxis in kidney transplant recipients [J]. Transplantation, 2011, 91(2): 251-255.
30. 　Sun HY, Waqener MM, Sinqh N. Prevention of posttransplant cytomegalovirus disease and related outcomes with valganciclovir: a systematic review[J]. Am J Transplant, 2008, 8(10): 2111-2118.
31. 　Alberú J, Morales-Buenrostro LE, Correa-Rotter R, et al. Long-term renal graft function and survival in patients with high-risk for cytomegalovirus infection receiving preemptive therapy[J]. Rev Invest Clin, 2008, 60(5): 365-374.
32. 　Small LN, Lau J, Snydman DR. Preventing post-organ transplantation cytomegalovirus disease with ganciclovir: a meta-analysis comparing prophylactic and preemptive therapies[J]. Clin Infect Dis, 2006, 43(7): 869-880.
33. 　Spinner ML, Saab G, Casabar E, et al. Impact of prophylactic versus preemptive valganciclovir on long-term renal allograft outcomes[J]. Transplantation, 2010, 90(4): 412-418.
34. 　Kliem V, Fricke L, Wollbrink T, et al. Improvement in long-term renal graft survival due to CMV prophylaxis with oral ganciclovir: results of a randomized clinical trial[J]. Am J Transplant, 2008, 8(5): 975-983.
35. 　Kalil AC, Levitsky J, Lyden E, et al. Meta-analysis: the efficacy of strategies to prevent organ disease by cytomegalovirus in solid organ transplant recipients[J]. Ann Intern Med, 2005, 143: 870-880.
36. 　Asberq A, Humar A, Rollaq H, et al. Oral valganciclovir is noninferior to intravenous ganciclovir for the treatment of cytomegalovirus disease in solid organ transplant recipients[J]. Am J Transplant, 2007, 7(9): 2106-2113.
37. 　郭紅梅. 巨細(xì)胞病毒耐藥性研究進(jìn)展[J]. 國(guó)外醫(yī)學(xué)·流行病學(xué)傳染病學(xué)分冊(cè), 2003, 30(3): 179-181.
38. 　Baldanti F, Lurain N, Gerna G. Clinical and biologic aspects of human cytomegalovirus resistance to antiviral drugs[J]. Hum Immunol, 2004, 65(5): 403- 409.
39. 　West P, Schmiedekamp M, Neeley H, et al. Use of high-dose ganciclovir for ganciclovir-resistant cytomegalovirus infection due to UL97 mutation[J]. Transpl Infect Dis, 2008, 10(2): 129-132.
40. 　Avery RK. Update in management of ganciclovir-resistant cytomegalovirus infection[J]. Curr Opin Infect Dis, 2008, 21(4): 433-437.
  1. 1. 　Humar A, Snydman D, AST Infectious Diseases Community of Practice. Cytomegalovirus in solid organ transplant recipients[J]. Am J Transplant，2009，9 (4): 78-86.
  2. 2. 　De Keyzer K, Van Laecke S, Peeters P, et al. Human cytomegalovirus and kidney transplantation: a clinician’s update[J]. Am J Kidney Dis, 2011, 58(1): 118-126.
  3. 3. 　Hu JH, Zhao H, Huang YP, et al. Opportunistic posttransplantation virus infections in renal transplant recipients[J]. Transplant Proc, 2011, 43(10): 3715-3719.
  4. 4. 　Fortun J, Martin-Davila P, Pascual J, et al. Immunosuppressive therapy and infection after kidney transplantation[J]. Transpl Infect Dis, 2010, 12(5): 397-405.
  5. 5. 　Tian JH, Wang X, Yang KH, et al. Induction with and without antithymocyte globulin combined with cyclosporine/tacrolimus-based immunosuppression in renal transplantation: a meta-analysis of randomized controlled trials[J]. Transplant Proc, 2009 , 41(9): 3671-3676.
  6. 6. 　Prichard MN, Kern ER. The search for new therapies for human cytomegalovirus infections[J]. Virus Res, 2011, 157(2): 212-221.
  7. 7. 　魏強(qiáng), 于立新, 鄧文鋒, 等. 腎移植術(shù)后感染巨細(xì)胞病毒性肺炎的多因素分析[J]. 南方醫(yī)科大學(xué)學(xué)報(bào), 2009, 29(6): 1182-1184.
  8. 8. 　Crough T, Khanna R. Immunobiology of human cytomegalovi-rus: from bench to bedside[J]. Clin Microbiol Rev, 2009, 2(1): 76-98.
  9. 9. 　Razonable RR, Paya CV. Herpesvirus infections in transplant recipients: current challenges in the clinical management of cytomegalovirus and epstein-barr virus infections[J]. Herpes, 2003, 10(3): 60-65.
  10. 10. 　滕東海, 田靜. 巨細(xì)胞病毒感染與腎移植[J]. 華西醫(yī)學(xué), 2003, 3(2): 411-412.
  11. 11. 　Dzabic M, Rahbar A, Yaiw KC, et al. Intragraft cytomegalovirus protein expression is associated with reduced renal allograft survival[J]. Clin Infect Dis, 2011, 53(10): 969-976.
  12. 12. 　Helanterä I, Loqinov R, Koskinen P, et al. Persistent cytomegalovirus infection is associated with increased expression of TGF-b 1, PDGF-AA and ICAM-1 and arterial intimal thickening in kidney allografts[J]. Nephrol Dial Transplant, 2005, 20(4): 790-796.
  13. 13. 　Reischiq T, Jindra P, Hes O, et al. Effect of cytomegalovirus viremia on subclinical rejection or interstitial fibrosis and tubular atrophy in protocol biopsy at 3 months in renal allograft recipients managed by preemptive therapy or antiviral prophylaxis[J]. Transplantation, 2009, 87(3): 436-444.
  14. 14. 　Hjelmesæth J, Sagedal S, Hartmann A, et al. Asymptomatic cytomegalovirus infection is associated with increased risk of new-onset diabetes mellitus and impaired insulin release after renal transplantation[J]. Diabetologia, 2004, 47(9): 1550-1556.
  15. 15. 　De Keyzer K, Van Laecke S, Peeters P, et al. Denovo thrombotic microangiopathy induced by cytomegalovirus infection leading to renal allograft loss[J]. Am J Nephrol, 2010, 32(5): 491-496.
  16. 16. 　Sagedal S, Hartmann A, Nordal KP, et al. Impact of early cytomegalovirus infection and disease on long-term recipient and kidney graft survival[J]. Kidney Int, 2004, 66(1): 329-337.
  17. 17. 　Kalis RS, Hudson SL, Gaston RS. Determinants of Cardiovascular Mortality After Renal Transplantation: A Role For Cytomegalovirus?[J]. Am J Transplant, 2003, 3(1): 79-81.
  18. 18. 　Kim CK, Song JH, Kim SM, et al. Clinical usefulness of human cytomegalovirus antigenemia assay after kidney transplantation[J]. Transplantation, 2003, 75(12): 2151-2155.
  19. 19. 　范文勇. 實(shí)時(shí)熒光定量-PCR和酶聯(lián)免疫吸附法檢測(cè)巨細(xì)胞病毒-IgM抗體的比較[J]. 醫(yī)學(xué)檢驗(yàn), 2011, 8(2): 83-85.
  20. 20. 　Rhee JY, Peck KR, Lee NY, et al. Clinical usefulness of plasma quantitative polymerase chain reaction assay: diagnosis of cytomegalovirus infection in kidney transplant recipients[J]. Transplant Proc, 2011, 43(7): 2624-2629.
  21. 21. 　Kotton CN, Kumar D, Caliendo AM, et al. International consensus guidelines on the management of cytomegalovirus in solid organ transplantation[J]. Transplantation, 2010, 89(7): 779-795.
  22. 22. 　Winston DJ, Young JA, Pullarkat V, et al. Maribavir prophylaxis for prevention of cytomegalovirus infection in allogeneic stem-cell transplant recipients: a multicenter, randomized, double-blind,placebo-controlled, dose-ranging study[J]. Blood, 2008, 111(11): 5403-5410.
  23. 23. 　Hodson EM, Jones CA, Webster AC, et al. Antiviral medications to prevent cytomegalovirus disease and early death in recipients of solid-organ transplants: a systematic review of randomized con-trolled trials[J]. Lancet, 2005, 365: 2105-2115.
  24. 24. 　Johnson RJ, Clatworthy MR, Brich R, et al. CMV mismatch does not affect patient and graft survival in UK renal transplant recipients[J]. Transplantation, 2009, 88(1): 77-82.
  25. 25. 　Chamberlain CE, Penzak SR, Alfaro RM, et al. Pharmacokinetics of low and maintenance dose valganciclovir in kidney transplant recipients[J]. Am J Transplant, 2008, 8(6): 1297-1302.
  26. 26. 　Humar A, Lebranchu Y, Vincenti F, et al. The efficacy and safety of 200 days valganciclovir cytomegalovirus prophylaxis in high-risk kidney transplant recipients[J]. Am J Transplant, 2010, 10(5): 1228-1237.
  27. 27. 　Humar A, Limaye AP, Blumberq EA, et al. Extended valganciclovir prophylaxis in D+/R- kidney transplant recipients is associated with long-term reduction in cytomegalovirus disease: two-year results of the IMPACT study[J]. Transplantation, 2010, 90(12): 1427-1431.
  28. 28. 　San Juan R, Yebra M, Lumbreras C, et al. A new strategy of delayed long-term prophylaxis could prevent cytomegalovirus disease in (D+/R-) solid organ transplant recipients[J]. Clin Transplant, 2009, 23(5): 666-671.
  29. 29. 　Boillat Blanc N, Pascual M, Venetz JP, et al. Impact of a preemptive strategy after 3 months of valganciclovir cytomegalovirus prophylaxis in kidney transplant recipients [J]. Transplantation, 2011, 91(2): 251-255.
  30. 30. 　Sun HY, Waqener MM, Sinqh N. Prevention of posttransplant cytomegalovirus disease and related outcomes with valganciclovir: a systematic review[J]. Am J Transplant, 2008, 8(10): 2111-2118.
  31. 31. 　Alberú J, Morales-Buenrostro LE, Correa-Rotter R, et al. Long-term renal graft function and survival in patients with high-risk for cytomegalovirus infection receiving preemptive therapy[J]. Rev Invest Clin, 2008, 60(5): 365-374.
  32. 32. 　Small LN, Lau J, Snydman DR. Preventing post-organ transplantation cytomegalovirus disease with ganciclovir: a meta-analysis comparing prophylactic and preemptive therapies[J]. Clin Infect Dis, 2006, 43(7): 869-880.
  33. 33. 　Spinner ML, Saab G, Casabar E, et al. Impact of prophylactic versus preemptive valganciclovir on long-term renal allograft outcomes[J]. Transplantation, 2010, 90(4): 412-418.
  34. 34. 　Kliem V, Fricke L, Wollbrink T, et al. Improvement in long-term renal graft survival due to CMV prophylaxis with oral ganciclovir: results of a randomized clinical trial[J]. Am J Transplant, 2008, 8(5): 975-983.
  35. 35. 　Kalil AC, Levitsky J, Lyden E, et al. Meta-analysis: the efficacy of strategies to prevent organ disease by cytomegalovirus in solid organ transplant recipients[J]. Ann Intern Med, 2005, 143: 870-880.
  36. 36. 　Asberq A, Humar A, Rollaq H, et al. Oral valganciclovir is noninferior to intravenous ganciclovir for the treatment of cytomegalovirus disease in solid organ transplant recipients[J]. Am J Transplant, 2007, 7(9): 2106-2113.
  37. 37. 　郭紅梅. 巨細(xì)胞病毒耐藥性研究進(jìn)展[J]. 國(guó)外醫(yī)學(xué)·流行病學(xué)傳染病學(xué)分冊(cè), 2003, 30(3): 179-181.
  38. 38. 　Baldanti F, Lurain N, Gerna G. Clinical and biologic aspects of human cytomegalovirus resistance to antiviral drugs[J]. Hum Immunol, 2004, 65(5): 403- 409.
  39. 39. 　West P, Schmiedekamp M, Neeley H, et al. Use of high-dose ganciclovir for ganciclovir-resistant cytomegalovirus infection due to UL97 mutation[J]. Transpl Infect Dis, 2008, 10(2): 129-132.
  40. 40. 　Avery RK. Update in management of ganciclovir-resistant cytomegalovirus infection[J]. Curr Opin Infect Dis, 2008, 21(4): 433-437.