The study aimed at analyzing the role of CMV infection as a risk factor for rejection occurring after CMV infection because of the clinical consequences of the prevention of CMV infection that might lead to the decrease in rejection episodes. Two hundred forty-two consecutive renal transplant patients were prospectively checked for the occurrence of CMV infection. CMV infection was defined virologically by a positive viremia or/and a positive viruria or/and a seroconversion or/and a significant rise of the anti-CMV antibody titers. Viremia, viruria, and serology were performed weekly for the first month and then at day 90, day 180, and every 6 months, and moreover if clinical symptoms related to a viral infection occurred. Rejection episode was defined by a creatininemia rise of 25%, after cyclosporine nephrotoxicity and urological complications had been discarded, and by the response to the antirejection therapy, steroids, or OKT3 in case of steroid-resistant rejection. 'rhe outcome factor was rejection episode occurring from day 4 after the diagnosis of CMV infection. A patient undergoing ''a rejection episode after CMV infection'' could also be exposed to other potential confounding factors that can be considered as risk factors of rejection among our patients. Rejection occurring before CMV infection was the main factor because it was linked both to CMV infection itself and to ''rejection after.'' Thus infected and noninfected patients were randomly paired off. To the noninfected patient of the pair was attributed the date of a fictitious CMV infection that was the date of the CMV infection of the infected member of the pair. Therefore, ''rejection after'' and ''rejection before'' were defined in infected and noninfected patients of the pair according to the time of onset of CMV infection of the infected member of the pair. The incidence of CMV infection was 65%, 157 of the 242 patients were infected, and 85 not infected. Thus 85 pairs of infected-noninfected patients were studied. The incidence of ''rejection after'' the diagnosis of CMV infection was significantly higher in the group of patients with (MV infection: 45% among infected (38/85) versus 10.60% among noninfected (9/85) (P< 0.0001). Among the 85 pairs, 48 pairs were concordant in which patient of the pair evinced the same outcome factor: 43 showed no rejection after, and 5 showed one. Among the 37 discordant pairs-''rejection after'' occurring in one patient only-the infected patient underwent the ''rejection after'' in 33 pairs, whereas the noninfected did in 4 pairs only, giving an odds ratio of 8.25 (95% confidence interval: 2.9-34). The following factors-''rejection before,'' donor and recipient CMV seropositivity, simultaneous kidney-pancreas transplantation, and HLA B and HLA DR matching-considered as potentially confounding because they were linked to the CMV infection, were taken into account in the analysis of the link between the CMV infection and rejection. After taking these 6 factors into account in a conditional logistic regression, the link between CMV infection and ''rejection after'' was not modified and remained significant That study showed that CMV infection is a risk factor of subsequent rejection episodes, previous rejection and other potential confounding factors being taken into account. The consequence is that prevention of the CMV infection by prophylactic measures might diminish the incidence of acute rejection episodes and chronic rejection and might improve the function and long-term survival of the renal graft.
