Mycophenolate mofetil does not modify the incidence of cytomegalovirus (CMV) disease after kidney transplantation but prevents CMV-induced chronic graft dysfunction.
Ganciclovir, which is used to treat cytomegalovirus (CMV) infection, has been shown in rodent models to abolish CMV-mediated chronic cellular damage and endothelial cell proliferation; when associated with mycophenolate mofetil (MMF), it has been shown to increase its anti-herpes virus activity. This study tested the hypothesis that kidney graft recipients who received antirejection prophylaxis with MMF and who were treated with ganciclovir for a declared CMV disease could be protected from chronic graft dysfunction. Investigated was the impact of ganciclovir-treated CMV diseases in consecutive first kidney recipients according to their immunosuppressive therapy. The azathioprine (Aza)-treated group (Aza group) included 319 patients. The MMF-treated group (MMF group) included 126 patients. CMV disease was clinically defined and confirmed by virological proof of CMV infection and was treated for at least 14 d with ganciclovir. Despite having the same incidence (21.6% in the Aza group versus 24.6% in the MMF group) and severity, CMV disease was significantly associated with graft loss independent of acute rejection episodes or other factors when tested in a Cox proportional model in the Aza group only (P < 10(-4)). It was shown for the first time that patients whose CMV disease is treated with ganciclovir while they are on MMF therapy are protected from the long-term deleterious consequences of CMV disease on graft survival, independent of acute rejection. It is suggested that the enhanced anti-herpes virus activity of ganciclovir by MMF could contribute to this reported effect, which may represent a significant contribution of MMF efficacy to graft survival.
Giral
Magali
M
Institut de Transplantation et de Recherche en Transplantation (ITERT) and INSERM U437, Nantes, France.
Nguyen
Jean Michel
JM
Service de Biostatistique, PIMEST, Nantes University Hospital, Nantes, France.
Daguin
Pascal
P
Institut de Transplantation et de Recherche en Transplantation (ITERT) and INSERM U437, Nantes, France.
Hourmant
Maryvonne
M
Institut de Transplantation et de Recherche en Transplantation (ITERT) and INSERM U437, Nantes, France.
Cantarovich
Diego
D
Institut de Transplantation et de Recherche en Transplantation (ITERT) and INSERM U437, Nantes, France.
Dantal
Jacques
J
Institut de Transplantation et de Recherche en Transplantation (ITERT) and INSERM U437, Nantes, France.
Blancho
Gilles
G
Institut de Transplantation et de Recherche en Transplantation (ITERT) and INSERM U437, Nantes, France.
Josien
Regis
R
Institut de Transplantation et de Recherche en Transplantation (ITERT) and INSERM U437, Nantes, France.
Ancelet
Daria
D
Institut de Transplantation et de Recherche en Transplantation (ITERT) and INSERM U437, Nantes, France.
Soulillou
Jean Paul
JP
Institut de Transplantation et de Recherche en Transplantation (ITERT) and INSERM U437, Nantes, France.
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D001379:Azathioprine / Q000627:therapeutic use; D002908:Chronic Disease; D003586:Cytomegalovirus Infections / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control*; D004359:Drug Therapy, Combination; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use; D006084:Graft Rejection / Q000821:virology; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015994:Incidence; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000517:prevention & control
D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D001379:Azathioprine; D015774:Ganciclovir