Factors Influencing Viral Clearance and Graft Outcomes Following Diagnosis of Polyomavirus BK-Associated Nephropathy After Renal Transplantation.

Purpose:The aim of this study is to identify factors influencing BK viral clearance and graft outcomes for Polyomavirus BK-associated nephropathy (BKVAN). Methods:Between 2006 and 2013, we diagnosed BKVAN in 39 (7.9%) of 491 patients with transplant biopsies by simian virus 40 (SV40) staining and quantitative polymerase chain reaction(PCR) assay for BKV DNA load in urine and plasma and quantitative assay of urine cytology. At diagnosis, we either reduced cyclosporine A by 30%(n=1), or reduced tacrolimus(Tac) by 30%-50%(n=22), or switched from Tac to cyclosporine A (n=13), or switched from Tac to Rapamycin(n=3). Data from these 39 patients were analyzed for graft functional decline, graft loss, graft survival rate, the time for viral PCR reduction in plasma by 1 log(90%) (≤7weeks or >7weeks), and influence factors. Results:During 28.5 ± 25.3 months follow-up, the frequencies of any short-term(3 months after diagnosis) functional decline, any long-term functional decline, and graft loss were 25.6%, 33.3%, and 25.6% respectively.The 1-, 3-, 5- graft survival rate were 100%, 77.4%, and 61.2%. More extensive interstitial inflammation(OR 9.020, p=0.027), but not viral load in blood and urine, nor the creatinine at diagnosis correlated with worse creatinine at 3 months. Viral reduction by 1 log was rapid in 51.4% (≤7 weeks) and slow in 48.6% (>7 weeks). On long-term follow-up, rapid viral reduction was associated with stable graft function(94.7%), compared with slow viral reduction (44.4%, p=0.001). Tac treatment had a negative influence on viral reduction time(OR 8.20, p=0.023). Defining 1-log viral load reduction as an event, Tac compared with non- Tac was associated with slow viral reduction (P=0.044).Multivariate analysis showed that extensive interstitial inflammation (HR 19.0, p=0.020) at diagnosis and slow viral reduction(HR 30.3, p=0.009) were associated with long-term functional decline. Clearance of viremia(78.4%) was associated with better graft survival at 3 years (89.2% versus 15.0%, p<0.001).Conclusions:Tac treatment prolongs BK viral reduction time. The extent of interstitial inflammation and viral reduction time influence short and long-term graft outcomes in patients with BKVAN.