Intragraft cytomegalovirus infection: a randomized trial of valacyclovir prophylaxis versus pre-emptive therapy in renal transplant recipients

Background: In a randomized study, we observed a higher incidence of biopsy-proven acute rejection with pre-emptive valganciclovir therapy as compared with valacyclovir prophylaxis for prevention of cytomegalovirus (CMV) disease after renal transplantation (RTx). Persistence of the virus within the allograft could stimulate the alloimmune response. The aim of our study was to evaluate intragraft CMV infection in patients randomized to the trial. Methods: RTx recipients at risk of CMV were randomized to pre-emptive therapy with valganciclovir (n=36) for significant CMV viraemia (>= 2,000 copies/ml by quantitative PCR in whole blood samples) or 3-month prophylaxis with valacyclovir (n=34). Renal biopsies performed during 12 months post-RTx were analysed for the presence of CMV by real-time PCR and immunohistochemical staining. Results: A total of 35 patients (59 biopsies) in the pre-emptive group and 31 patients (57 biopsies) with valacyclovir prophylaxis had biopsy specimen with sufficient material for intragraft CMV determination. Cumulative incidence of intragraft CMV infection was 14% and 7% (P=0.315) with pre-emptive therapy and prophylaxis, respectively. Patients at risk for primary CMV infection (CMV serological donor-positive and recipient-negative) were at higher risk for intragraft CMV infection (40% versus 5%; P=0.008). CMV viraemia at the time of biopsy was associated with the presence of CMV within the allograft (P<0.001). Conclusions: During the first year after RTx, the incidence of intragraft CMV infection was relatively low with comparable rates in patients managed by pre-emptive valganciclovir therapy and valacyclovir prophylaxis.