Graph showing typical course of viruria, viremia, and BK-induced nephropathy

Prototypical course of BKPyVAN and opportunities for timely intervention. The vast majority of cases of BKPyVAN are preceded by an asymptomatic period of persistent and significant Vr. This can be demonstrated by PCR-based studies (>10E+05 viral copies/mL) or by urine cytology (decoy cells present for 2 or more months). Both BKPyV and JCPyV Vr manifest with decoy cells, but only BKPyV Vr increases the risk for graft loss or shortened graft survival. Sustained BKPyV Vr is typically followed within weeks by the development of Vm. Significant, sustained Vm (>5000 BKPyV copies/mL for 3 consecutive weeks) characterizes patients with high, uncontrolled viral replication, leading to parenchymal injury. Progression of BKPyVAN leads to eventual deterioration of the graft function. In patients with uncomplicated BKPyVAN, appearance of Vr and Vm precede the increase in serum creatinine by weeks or months.
Histologic diagnosis of BKPyVAN (positive biopsy). The statistical possibility to achieve a histologic diagnosis by needle graft biopsy is directly proportional to the time elapsed from the initiation of the Vm and correlates with the overall level of viral loads (Vr, Vm). Negative biopsy samples are common in early BKPyVAN due to heterogeneous renal involvement. Longer and more pronounced Vm is associated with more severe histologic disease/pattern and larger number of cells with viral cytopathic changes (SV40+ cells).
(E-G) Options for clinical intervention in BKPyVAN:
(E) Preemptive intervention. In patients with Vr and Vm, progressive and customized decrease in immunosuppression before significant renal scarring has occurred leads to resolution of the infection in 85 to 90% of cases, with long-term preservation of graft function. Risk of acute rejection is low (10 to 15%). Intervention is not indicated in the absence of Vm (ie, Vr only).
(F) Obligatory intervention. Late diagnosis and intervention once graft dysfunction is evident decreases the likelihood of viral clearance and is associated with higher rates of premature graft loss (30 versus 10%).
(G) Ineffectual, late intervention. The late stage of BKPyVAN resembles clinically and histologically end-stage kidney disease from other causes. With progressive obliteration of the renal tubules (the primary target of BKPyV infection) there is progressive decrease of Vr and Vm.