CYTOMEGALOVIRUS-INFECTION - AN ETIOLOGIC FACTOR FOR REJECTION - A PROSPECTIVE-STUDY IN 242 RENAL-TRANSPLANT PATIENTS

The study aimed at analyzing the role of CMV infection as a risk facto r 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 ren al transplant patients were prospectively checked for the occurrence o f CMV infection. CMV infection was defined virologically by a positive viremia or/and a positive viruria or/and a seroconversion or/and a si gnificant 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 relate d to a viral infection occurred. Rejection episode was defined by a cr eatininemia rise of 25%, after cyclosporine nephrotoxicity and urologi cal complications had been discarded, and by the response to the antir ejection therapy, steroids, or OKT3 in case of steroid-resistant rejec tion. 'rhe outcome factor was rejection episode occurring from day 4 a fter the diagnosis of CMV infection. A patient undergoing ''a rejectio n episode after CMV infection'' could also be exposed to other potenti al confounding factors that can be considered as risk factors of rejec tion 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 r andomly paired off. To the noninfected patient of the pair was attribu ted the date of a fictitious CMV infection that was the date of the CM V infection of the infected member of the pair. Therefore, ''rejection after'' and ''rejection before'' were defined in infected and noninfe cted patients of the pair according to the time of onset of CMV infect ion 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 incid ence of ''rejection after'' the diagnosis of CMV infection was signifi cantly higher in the group of patients with (MV infection: 45% among i nfected (38/85) versus 10.60% among noninfected (9/85) (P< 0.0001). Am ong the 85 pairs, 48 pairs were concordant in which patient of the pai r evinced the same outcome factor: 43 showed no rejection after, and 5 showed one. Among the 37 discordant pairs-''rejection after'' occurri ng in one patient only-the infected patient underwent the ''rejection after'' in 33 pairs, whereas the noninfected did in 4 pairs only, givi ng an odds ratio of 8.25 (95% confidence interval: 2.9-34). The follow ing factors-''rejection before,'' donor and recipient CMV seropositivi ty, simultaneous kidney-pancreas transplantation, and HLA B and HLA DR matching-considered as potentially confounding because they were link ed to the CMV infection, were taken into account in the analysis of th e link between the CMV infection and rejection. After taking these 6 f actors into account in a conditional logistic regression, the link bet ween CMV infection and ''rejection after'' was not modified and remain ed significant That study showed that CMV infection is a risk factor o f subsequent rejection episodes, previous rejection and other potentia l confounding factors being taken into account. The consequence is tha t prevention of the CMV infection by prophylactic measures might dimin ish the incidence of acute rejection episodes and chronic rejection an d might improve the function and long-term survival of the renal graft .