Impact of early cytomegalovirus infection and disease on long-term 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.

Pre-emptive therapy of CMVpp65 antigen positive renal transplant recipients with oral ganciclovir: a randomized, comparative study.

BACKGROUND: About one-quarter of renal transplant patients will suffer from symptomatic cytomegalovirus (CMV) disease if no preventive therapeutic measures are taken. In this prospective, randomized single-centre study pre-emptive therapy with oral ganciclovir is compared with conventional deferred treatment. METHODS: Renal transplant recipients (n= 455) over 18 years of age were screened weekly for CMV pp65 antigenaemia during the first 12 weeks post-transplantation. If CMV pp65 antigen in leukocytes appeared within 8 weeks post-transplantation patients were randomized and included in the study. Five patients developed CMV disease before positive CMV pp65, and 14 patients with a positive antigen test developed CMV disease before randomization could take place, all these representing a limitation of the applicability of the results in the overall renal transplant population. Altogether 179 patients were not randomized for various reasons. Eighty patients completed the study, 42 were randomized to receive pre-emptive oral ganciclovir therapy and 38 to conventional deferred treatment (control group). RESULTS: Time from transplantation to start of ganciclovir capsules was 36 (12-60) days and duration of oral ganciclovir therapy was 49 (27-70) days, median (range). No patient in the pre-emptive treatment group, but nine of 38 patients (23.7%) in the control group, developed CMV disease during the first 12 weeks post-transplantation (P= 0.0009). In the period from 3 months to 1 year post-transplantation, two patients in each group developed CMV disease. There were no significant differences in acute rejection or renal function between treatment groups during the first post-transplant year. CONCLUSIONS: Pre-emptive oral ganciclovir therapy in renal transplant recipients during the first 12 weeks post-transplantation effectively prevents CMV disease during this time period. The incidence of late CMV disease (3 months to 1 year after transplantation) was similar in the two groups, indicating that pre-emptive therapy does not result in late onset of CMV disease.

The impact of cytomegalovirus infection and disease on rejection episodes in renal allograft recipients.

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 = 1.6 (1.1-2.5, p = 0.02) and RR = 2.5 (1.2-5.1, p = 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 = 3.1 (1.1-9.3, p = 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.