Intravenous ganciclovir is the standard treatment for cytomegalovirus disease in solid organ transplant recipients. Oral valganciclovir is a more convenient alternative. In a randomized, international trial, recipients with cytomegalovirus disease were treated with either 900 mg oral valganciclovir or 5 mg/kg i. Oral valganciclovir shows comparable safety and is not inferior to i.v. ganciclovir for treatment of cytomegalovirus disease in organ transplant recipients and provides a simpler treatment strategy, but care should be taken in extrapolating to organ transplant recipients not properly represented in the present study.

Impact of early cytomegalovirus infection and disease on longterm recipient and kidney graft survival.Background. The impact of cytomegalovirus (CMV) infection and disease on long-term outcome after kidney transplantation is still unsettled.Methods. Between 1994 and 1997, 397 consecutive first kidney graft recipients and 74 retransplants were included in the study and followed prospectively until December 31, 2001. CMV infection (CMV pp65 antigenemia) and CMV disease were recorded once weekly during the first 100 days after transplantation. No CMV prophylaxis or preemptive therapy was given. In a multiple Cox proportional hazard model allowing time-dependent covariates, the effects of asymptomatic CMV infection and CMV disease, recipient age and gender, retransplantation, living donor, panel-reactive cytotoxid antibodies, acute rejection, and graft loss were tested on overall mortality beyond 100 days post-transplantation. In a similar analysis, the effect of asymptomatic CMV infection and CMV disease plus other factors were tested on death censored graft loss beyond 100 days.Results. Median (range) follow up time was 66.6 (<1-86.9) months. The incidence of CMV infection and disease during the first 100 days was 62.8% and 23.4%, respectively. The number of total deaths was 96 (20%), 82 occurred after the first 100 days. Independent risk factors for overall mortality beyond 100 days were asymptomatic CMV infection, RR = 2.90 (95% CI 1.61-5.22) (P = 0.001), CMV disease, RR = 2.50 (95% CI 1.31-4.79) (P = 0.006), both compared to no infection or disease, recipient age, RR = 1.066 per year (95% CI 1.048-1.084) (P < 0.001), and graft loss in the whole study period RR = 7.88 (95% CI 4.75-13.08) (P < 0.001). Asymptomatic CMV infection and CMV disease were not independent risk factors for death censored graft loss, but they significantly reduced graft survival uncensored for death, (log rank P = 0.001, respectively).Conclusion. Asymptomatic CMV infection and overt CMV disease during the first 100 days increase the risk of recipient mortality beyond 100 days. This raises the question whether CMV prophylaxis should be given routinely after kidney transplantation.

Cytomegalovirus (CMV) infection and disease are potential risk factors for acute allograft rejection in renal transplant recipients. The present study specifically addresses this issue. From October 1994 to July 1997, 477 consecutive renal allograft recipients (397 first transplants and 80 retransplants) were included in the study. CMV infection (cytomegalovirus pp65 antigen in leukocytes) and disease (infection and clinical symptoms or signs of disease) were examined prospectively for 3 months. No CMV prophylaxis was given, and CMV disease was treated with intravenous (i.v.) ganciclovir. The retransplantation of four patients transplanted twice during the study and 22 patients receiving kidneys from human leucocyte antigen (HLA)-identical siblings were excluded from statistical analysis. Rejections were evaluated clinically [277(61%)] and 173 (38%) also had a biopsy verified rejection. CMV infection occurred in 64% of the patients and 24% experienced CMV disease. In a multiple time-dependent Cox analysis, CMV infection and CMV disease were independent significant predictors for clinical acute rejections, RR Ω 1.6 (1.1-2.5, p Ω 0.02) and RR Ω 2.5 (1.2-5.1, p Ω 0.01), respectively. Among 173 patients with biopsy verified rejection, 72% of the patients had tubulointerstitial rejection whereas 28% had a vascular rejection. CMV disease, but not CMV infection was a predictor of tubulointerstitial rejection, RR Ω 3.1 (1.1-9.3, p Ω 0.04). CMV infection and disease are independent risk factors for clinical acute rejection in kidney allograft recipients. CMV disease is an independent risk factor for biopsy verified acute tubulointerstitial rejection in kidney allograft recipients.

Aims/hypothesis. The human cytomegalovirus (CMV) may increase the risk of diabetes mellitus, but the literature is scarce. The present study was designed to test the hypothesis that asymptomatic CMV infection is associated with increased risk of new-onset diabetes after renal transplantation, and to assess the impact of asymptomatic CMV infection on OGTT-derived estimates of insulin release and insulin action. Methods. A total of 160 consecutive non-diabetic renal transplant recipients on cyclosporine (Sandimmun Neoral)-based immunosuppression were closely monitored for CMV infection during the first 3 months after transplantation. All patients underwent a 75-g OGTT at 10 weeks. Excluded from the analyses were 36 patients with symptomatic CMV infection (disease).Results. The incidence of new-onset diabetes was 6% in a control group of recipients without CMV infection (4/63) and 26% in the group with asymptomatic CMV infection (16/61). Asymptomatic CMV infection was associated with a significantly increased risk of new-onset diabetes (adjusted odds ratio: 4.00; 95% CI: 1.19 to 13.43, p=0.025). The group of patients with CMV infection had a significantly lower median insulin release than controls. Conclusions/interpretation. Our findings support the hypothesis that asymptomatic CMV infection is associated with increased risk of new-onset post-transplant diabetes mellitus, and suggest that impaired insulin release may involve one pathogenetic mechanism.

The incidence of CMV infections in first transplants was 68% in D+R- and D+/-R+ serostatus groups, whereas the incidence of CMV disease was higher in D+R- (56%) than in D+/-R+ (20%, P<0.001). No difference in severity of CMV disease in D+R- and D+/-R+ was seen except for an increased incidence of hepatitis in primary infections. One of 14 deaths could be associated with CMV disease in a seropositive recipient. Cox regression analysis showed that rejection (RR 2.5, P<0.01) and serostatus group D+R- (RR 3.9, P<0.001) were significant risk factors for development of CMV disease. The maximum CMV pp65 antigen count had significant correlation to disease only in CMV seropositive recipients, P<0.001. Conclusion. Renal transplant recipients can safely be given deferred ganciclovir therapy for CMV disease if they are intensively monitored for CMV infection. Patients with primary CMV infection (D+R-), CMV infected patients undergoing anti-rejection therapy and R+ patients with high CMV pp65 counts seem to have a particular potential for benefit from preemptive anti-CMV-therapy.