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 be en shown in rodent models to abolish CMV-mediated chronic cellular damage a nd endothelial cell proliferation; when associated with mycophenolate mofet il (MMF), it has been shown to increase its anti-herpes virus activity. Thi s study tested the hypothesis that kidney graft recipients who received ant irejection prophylaxis with MMF and who were treated with ganciclovir for a declared CMV disease could be protected from chronic graft dysfunction; In vestigated was the impact of ganciclovir-treated CMV diseases in consecutiv e first kidney recipients according to their immunosuppressive therapy. The azathioprine (Aza)-treated group (Aza group) included 319 patients. The MM F-treated group (MMF group) included 126 patients. CMV disease was clinical ly defined and confirmed by virological proof of CMV infection and was trea ted 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 dis ease was significantly associated with graft loss independent of acute reje ction 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 patient s whose CMV disease is treated with ganciclovir while they are on MMF thera py are protected from the long-term deleterious consequences of CMV disease on graft survival, independent of acute rejection. It is suggested that th e enhanced anti-herpes virus activity of ganciclovir by MMF could contribut e to this reported effect, which may represent a significant contribution b f MMF efficacy to graft survival.