title: Mycophenolate mofetil does not modify the incidence of cytomegalovirus (CMV) disease after kidney transplantation but prevents CMV-induced chronic graft dysfunction.
abstract: 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.
authors.affiliation: Institut de Transplantation et de Recherche en Transplantation (ITERT) and INSERM U437, Nantes, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Giral
authors.affiliation: Service de Biostatistique, PIMEST, Nantes University Hospital, Nantes, France.
authors.forename: Jean Michel
authors.initials: JM
authors.lastname: Nguyen
authors.affiliation: Institut de Transplantation et de Recherche en Transplantation (ITERT) and INSERM U437, Nantes, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Daguin
authors.affiliation: Institut de Transplantation et de Recherche en Transplantation (ITERT) and INSERM U437, Nantes, France.
authors.forename: Maryvonne
authors.initials: M
authors.lastname: Hourmant
authors.affiliation: Institut de Transplantation et de Recherche en Transplantation (ITERT) and INSERM U437, Nantes, France.
authors.forename: Diego
authors.initials: D
authors.lastname: Cantarovich
authors.affiliation: Institut de Transplantation et de Recherche en Transplantation (ITERT) and INSERM U437, Nantes, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Dantal
authors.affiliation: Institut de Transplantation et de Recherche en Transplantation (ITERT) and INSERM U437, Nantes, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Blancho
authors.affiliation: Institut de Transplantation et de Recherche en Transplantation (ITERT) and INSERM U437, Nantes, France.
authors.forename: Regis
authors.initials: R
authors.lastname: Josien
authors.affiliation: Institut de Transplantation et de Recherche en Transplantation (ITERT) and INSERM U437, Nantes, France.
authors.forename: Daria
authors.initials: D
authors.lastname: Ancelet
authors.affiliation: Institut de Transplantation et de Recherche en Transplantation (ITERT) and INSERM U437, Nantes, France.
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Soulillou
mesh_terms: 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
chemical_list: D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D001379:Azathioprine; D015774:Ganciclovir