The balance between over- and under-immunosuppression is crucial for graft and overall survival after kidney transplantation (KTX). Too much immunosuppression (IS) predisposes to opportunistic infections, including viral infections by Cytomegalovirus (CMV), BK virus (BKV) or Epstein-Barr virus (EBV). Each can inflict virus-specific primary diseases (i.e., CMV infection of different organs) but may also result in graft loss (especially BK nephropathy) or post-transplant lymphoproliferative disease (PTLD, i.e., EBV-associated).[1]

The Torque Teno Virus (TTV) of the Anelloviridae family is a non-pathogenic and ubiquitous virus in humans.[2] Its load in the blood is associated with the immune state of its host as demonstrated by an increasing number of studies including in solid organ transplanted patients.[3,4] In adult patients with KTX, lower TTV levels were associated with an increased risk for antibody-mediated rejection[5] and patients with infectious complications showed higher TTV levels[6]. In a recent study we demonstrated that also in pediatric KTX patients plasma TTV load is associated with the type of IS regimen as well as prednisolone or mycophenolate mofetil dose.[7] These results confirmed associations of TTV load with IS during follow-up after transplantation that have been demonstrated in adult patients. Correlation of TTV plasma loads to clinical events linked to the intensity of IS (i.e., opportunistic infections) has not yet been demonstrated in pediatric KTX patients.

Therefore, the aim of this study was to investigate whether TTV loads could predict major opportunistic viral infections in children and adolescents after KTX. We primarily focused on the prediction of clinically relevant CMV infection as a directly treatable post-KTX complication. Secondarily we aimed to investigate the prediction of TTV loads for other major opportunistic viral infections (i.e., BKV and EBV) and associations of plasma and/or urine loads of all three viruses with TTV plasma loads during follow-up.