Subclinical cytomegalovirus and Epstein–Barr virus viremia are associated with adverse outcomes in pediatric renal transplantation

Abstract: Post-transplant clinical disease with cytomegalovirus (CMV) and Epstein–Barr virus (EBV) is a known risk factor for graft dysfunction and lymphoproliferation. We postulate that subclinical, asymptomatic viremia also adversely impacts outcomes, and may warrant re-assessment of current monitoring and antiviral prophylaxis protocols. A single-center study was conducted on 102 pediatric (51 steroid-free and 51 matched steroid-based historical controls). Quantitative viral loads were serially monitored and correlated with outcome measures. Overall, the incidence of CMV and EBV clinical disease was 5% (1% CMV and 4% EBV); however, the incidence of subclinical viremia was 44% (12.7% CMV, 38.2% EBV, 6.9% CMV + EBV). Risk factors for subclinical viremia were EBV naivety (p = 0.07), age less than five yr (p = 0.04), lack of prophylaxis (p = 0.01), and steroid usage (p = 0.0007). Subclinical viremia was associated with lower three-yr graft function (p = 0.03), increased risk of acute rejection (odds ratio 2.07; p = 0.025), hypertension (p = 0.04), and graft loss (p = 0.03). Subclinical asymptomatic CMV and EBV viremia is a risk factor for graft injury and loss. These findings support the need for aggressive, serial viral monitoring to better determine the appropriate length of post-transplant antiviral prophylaxis, and to determine the effect of immunosuppression protocols on the development of viremia.