Delayed-onset primary cytomegalovirus disease and the risk of allograft failure and mortality after kidney transplantation

Background. During the contemporary era of antiviral prophylaxis, the impact of delayed-onset primary cytomegalovirus (CMV) disease on the outcome of kidney transplantation is not known. We evaluated the incidence, clinical features, risk factors, and outcomes of CMV disease among high-risk kidney transplant recipients. Methods. The medical records of CMV-seronegative recipients of kidney transplants from CMV-seropositive donors were reviewed. Cox proportional hazards regression was used to identify factors associated with CMV disease and to assess its impact on allograft loss and mortality. Results. None of the 176 CMV-seronegative recipients of kidney transplants from CMV-seropositive donors developed breakthrough CMV disease during a median of 92 days (interquartile range, 90-92 days) of oral ganciclovir or valganciclovir prophylaxis. Thereafter, 51 patients (29%) developed CMV disease at a median of 61 days (interquartile range, 40-143 days) after stopping antiviral prophylaxis. Early-onset bacterial and fungal infection (hazard ratio, 3.61; 95% confidence interval, 1.78-7.33; P < .001) and a Charlson comorbidity index ≥3 (hazard ratio, 2.21; 95% confidence interval, 1.15-4.22; P = .011) were associated with a higher risk of delayed-onset primary CMV disease, and postrejection antiviral prophylaxis (hazard ratio, 0.29; 95% confidence interval, 0.09-0.94; P = .039) was associated with a lower risk of such CMV disease. A time-dependent Cox regression analysis revealed a statistically significant association between tissue-invasive CMV disease and allograft loss or mortality (hazard ratio, 2.85; 95% confidence interval, 1.22-6.67; P = .016). Conclusion. This study of a large cohort of CMV-seronegative recipients of kidney transplants from CMV-seropositive donors illustrates the ongoing challenge of delayed-onset primary CMV disease and its impact on transplantation outcomes despite antiviral prophylaxis. Better strategies for CMV disease prevention after kidney transplantation are warranted.