Predictive value of torque teno virus viral load for BK polyomavirus DNAemia depends on BK polyomavirus-specific humoral immunity in kidney transplant recipients.

Neutralizing antibodies (NAbs) have been proposed as biomarkers for stratifying BK polyomavirus (BKPyV) replication risk, while torque teno virus (TTV) viral load is recognized as a global immunomarker in kidney transplantation. This study investigates their combined utility to improve BKPyV DNAemia risk assessment in 187 patients within 12 months posttransplant. BKPyV DNAemia occurred in 19% of recipients. Donor seronegativity was protective, whereas in case of seropositive donor, replication risk varied according to recipient NAb titers. Indeed, patients with low NAbs faced a high risk of BKPyV DNAemia regardless of TTV load, whereas in those with high NAbs, replication was influenced by TTV load at 1 month posttransplant. These findings provide a deeper understanding of BKPyV infection in kidney transplant recipients. In patients with low humoral immunity, the risk of early replication is high, whereas in those with adequate humoral immunity, replication appears to be primarily driven by the overall burden of immunosuppression. Donor status and cold ischemia time were also associated with BKPyV DNAemia, suggesting an influence of transplant characteristics and related injury. Our findings support a multifactorial BKPyV risk assessment integrating immune markers to enable personalized prevention and potentially reduce BKPyV risk.