Treatment of BK Viremia and Subsequent Graft Rejecttion - A Double-Edged Sword Clinical Decision.

Abstract

Various reports have described clinical activity of leflunomide (Lf) and ciprofloxacin toward clearing BK viremia (BKV). Moreover, both drugs are thought to have immunosuppressive effect that might protect against graft rejection after reduction of standard immunosuppression. There are limited data comparing BKV clearance rates and incidence of subsequent graft rejection after using these drugs. The aim of this study was to compare the rate of BKV clearance and the incidence of subsequent graft rejection following the use of different BKV treatment protocols. We screened 609 kidney recipients from 2007 to 2011 for BKV using qPCR in blood. During 1-year following transplant, 130 patients (21.3%) had BKV. 91% of our cohort had protocol biopsy done (at 0, 3, or 12 months post-transplant). Moreover, patients with BKV and impaired graft function had for-cause biopsy. We classified patients with BKV by the treatment received into: Observation (n=44); reduction in immunosuppression (RIS) (30-50% reduction) (n=43); RIS + Cipro (n=14); RIS + Lf (n=18); or RIS + Cipro + Lf (n=11). We compared the slopes of decline of BKV among the groups. We also recorded the incidence of biopsy proven acute graft rejection (BPAR) that occurred after initiating the treatment. The 5 slopes were parallel to each other with no significant difference in the rate of BKV decline (p=0.16). Eleven of 130 (8.5%) patients with BKV developed BPAR within a median of 1.9 months after initiating BKV treatment (IQR 1.2-9.8) compared to 39/479 (8.1%) in patients without BKV (p=0.9). There was a trend toward graft rejection in the group who had RIS alone (11.6%), compared to the groups who had cipro (7%), Lf (5.8%), cipro + Lf (9%) or observation (6.6%) using the Cox survival model (p= 0.9). The evidence does not support increased viral clearance when Lf and/or cipro are added to RIS. Moreover, adding Lf and/or cipro to the RIS was not associated with a significant lower risk of subsequent BPAR. Larger prospective studies are still needed to confirm these results.