Polyomavirus BK replication dynamics in vivo and in silico to predict cytopathology and viral clearance in kidney transplants

Fast BK virus (BKV) replication in renal tubular epithelial cells drives polyomavirus-BK-associated nephropathy (PVAN) to premature kidney transplant (KT) failure. BKV also replicates in urothelial cells, but remains asymptomatic in two-thirds of affected KT patients. Comparing 518 day-matched plasma-urine samples from 223 KT patients, BKV loads were approximately 3000-fold higher in urine than in plasma (p 95% of urine BKV loads resulted from urothelial replication and 80% was required for clearing viremia within 7 weeks, but viruria persisted for <14 weeks. Reductions <90% cleared viremia and viruria by 3 and 10 weeks, respectively. The model was clinically validated in prospectively monitored KT patients supporting <80% curtailing for optimal interventions.