Association between cytomegalovirus disease and chronic rejection in kidney transplant recipients

Background. It has long been suggested that cytomegalovirus (CMV) disease p lays a role in the pathogenesis of chronic rejection (CR), However, its rol e has been difficult to prove, given the strong association between acute r ejection and CMV, and the even stronger association between acute rejection and CR, To try to isolate the relative contribution of CMV infection in th e pathogenesis of CR, we used multivariate techniques to examine risk facto rs for CR, including CMV disease. Methods. Our study population consisted of adult recipients of a first kidn ey graft who underwent transplantation at a single center between 1/1/85 an d 6/30/97 (n=1339). Results. Multivariate analysis using time to CR as the dependent variable d emonstrated acute rejection to be the strongest risk. factor (relative risk [RR]=17.8, P=0.0001), followed by older donor age (RR=1.46, P=0.01). The p resence of CMV disease showed a trend toward increased risk for CR (RR=1.30 , P=0.10), although the association was not as strong as with the other two variables. Comparing only those recipients with acute rejection and CMV di sease versus those with acute rejection but no CMV disease, the relative ri sk of developing CR was 1.37 times higher in the former group. Recipients w ith acute rejection and CMV developed CR sooner and with a higher incidence versus those with acute rejection but no CMV (P=0.002). It is interesting, however, that CMV disease was only a risk factor for CR in the presence of acute rejection. Recipients with no acute rejection and CMV disease did no t have a higher incidence of CR versus those with no acute rejection and no CMV (P=NS). Conclusion. CMV disease seems to play some role in the pathogenesis of CR b ut only in the presence of acute rejection. Reasons may include (i) the ina bility to adequately treat acute rejection due to the presence of CMV disea se or (ii) the increased virulence of latent CMV virus in recipients being treated for acute rejection. Our data may suggest a role for more aggressiv e prophylaxis against CMV disease, especially at the time of treatment for acute rejection.