Case Report: Late-onset BK polyomavirus-associated nephropathy in kidney transplant recipients: two cases and insights into underlying mechanisms.

BK polyomavirus-associated nephropathy (BKPyVAN) results from primary infection or reactivation of BK polyomavirus (BKPyV) and remains a significant complication in kidney transplant recipients, contributing to allograft dysfunction and premature allograft loss. Most cases occur within the first 2 years post-transplant, when cell-mediated immunity is most suppressed due to induction immunosuppression. Here, we describe two unusual cases of late-onset BKPyVAN occurring in the absence of intensified immunosuppression and provide a review of potential mechanisms underlying its development in kidney transplant recipients. In the first patient, BKPyVAN developed 9 years after transplantation during maintenance dual immunosuppression with tacrolimus and mycophenolic acid, without prior rejection episodes or exposure to intensified immunosuppression. In the second patient, BKPyVAN first occurred 3 years post-transplant in the setting of concomitant cytomegalovirus colitis, also during dual immunosuppression with tacrolimus and mycophenolic acid. Despite reduction of immunosuppression, BKPyVAN persisted at 1-year follow-up and was associated with a gradual decline in allograft function. These cases highlight that late-onset BKPyVAN may develop even without intensified immunosuppression and can lead to significant allograft injury. Improved strategies are needed to identify patients at risk for late-onset BKPyVAN and to optimize therapeutic management.