Cytomegalovirus-related disease and risk of acute rejection in renal transplant recipients: a cohort study with case-control analyses.

The relationship between a cytomegalovirus (CMV) infection and the acute rejection of a renal transplant is not well established. The aim of the study was to document whether the clinical presentation of a CMV infection as a diffuse inflammatory disease or as a clinically asymptomatic illness is a risk factor of acute renal transplant rejection. One hundred and ninety-two consecutive renal transplant recipients were included in a historical cohort study for exposed-non exposed analyses. CMV infection after transplantation was the exposure factor. Before transplantation, 113 patients had antibodies against CMV and 79 were seronegative. The patients were divided into three groups: Group 1 consisted of 64 patients who had neither clinical signs of CMV disease nor CMV serological changes after transplantation, Group 2 consisted of 77 seropositive patients with asymptomatic viremia, and Group 3 consisted of 51 seropositive patients with clinical signs of diffuse inflammation that included fever, neutropenia, and various visceral involvements (CMV disease). Groups 2 and 3, the seropositive patients, were paired with Group 1 patients. Acute rejection was considered as CMV-induced when it occurred within one month following viremia, during the first year after transplantation. Transplant patients with CMV disease, had a significant likelihood of developing acute rejection after CMV infection or reactivation (P < 0.01). The odds ratio for developing rejection was 5.98, 95% confidence interval: 1.21-29.40. Such a link was not documented for recipients with asymptomatic CMV infection. In conclusion, CMV disease, but not asymptomatic viremia, is a risk factor of acute renal transplant rejection. On epidemiological grounds, these results support the hypothesis that factors controlling both the viral replication and the diffuse inflammatory process are implicated in acute graft rejection.

[Cytomegalovirus infection, a risk factor for acute graft rejection in renal transplant recipients. A case-controlled study]. / La maladie à cytomégalovirus, facteur de risque de rejet aigu d'allogreffe rénale. Etude exposés/non exposés.

OBJECTIVES: We studied the relationship between cytomegalovirus infection and episodes of acute rejection after infection in renal graft recipients at the Reims University Hospital from 1989 to 1995. PATIENTS AND METHODS: Two exposed versus nonexposed analyses were conducted, one (series 1) for CMV infection and the other (series 2) for CMV disease. For each analysis, exposed recipients were matched with nonexposed recipients for date of graft (+/- 6 months). Risk of acute rejection was assessed with univariate analysis then with multivariate analysis using logistic regression. RESULTS: Among the 192 graft recipients included, 64 developed CMV infection, 77 had an infection (series 1) and 51 had CMV disease (series 2). In series 1, only failure of renal graft was a significant risk factor of acute rejection (OR = 10.4; 95% Cl 1.9-56.3). CMV infection was not a significant risk factor (OR = 1.06; 95% Cl 0.2-5.6). Conversely, in series 2, there was a 6-fold increase in the risk of acute rejection in recipients who developed CMV disease (OR = 5.98; 95% Cl 1.21-29.4). CONCLUSION: The fact that CMV disease and not CMV infection is a risk factor of acute rejection in renal transplant recipients is an argument for implicating a general inflammatory reaction characteristic of CMV disease in the pathogenesis of acute rejection. This finding favors preventive treatment of CMV infection.