No clinical benefit of rapid versus gradual tapering of immunosuppression to treat sustained BK virus viremia after kidney transplantation: a single‐center experience

Abstract

Summary Immunosuppressive drug tapering is currently the recommended treatment of BK virus (BKV) viremia after kidney transplantation; however, its exact modalities remain unclear. We retrospectively compared two consecutive strategies in 111 patients with sustained viremia: a gradual monitoring/tapering group (GT, n = 57) before 2012 and a rapid monitoring/tapering group (RT, n = 54) after 2012. At viremia diagnosis, the dose of mycophenolic acid (MPA) and tacrolimus levels (T0) were similar among patient groups. However, following onset, the dose of MPA at 1 month (P = 0.002) and 3 months (P = 0.005) and Tac T0 at 1 month (P = 0.030) and 3 months (P = 0.006) were lower in the RT group. This rapid minimization shortened BKV viremia (P < 0.001) and resulted in a better protection of graft function in patients with confirmed BKV‐associated nephropathy (P = 0.033) without impacting 5‐year graft survival. Survival without rejection was similar (P = 0.571), but the RT group had increased the development of de novo donor‐specific antibodies (dnDSAs; P < 0.001). Multivariate Cox analysis identified basiliximab versus Thymoglobulin® induction [hazard ratio (HR), 3.090; P = 0.001] and the RT strategy (HR, 6.021; P = 0.002) as independently associated with dnDSAs. Compared to a gradual tapering, rapid immunosuppression tapering to treat sustained BKV viremia does not improve medium‐term clinical outcome but increases the risk of developing dnDSAs.

Increasing net immunosuppression after BK polyoma virus infection

“…The 21.6% incidence of BKV observed was consistent with other reports where similar immunosuppression protocols were used 8,12 . In addition, the rates of BPAR and de novo DSA were within the ranges referenced in the literature, 12%‐50% and 3.3%‐79%, respectively 8–12,16 . The incidence of antibody‐medication rejection may have been underestimated by our study since the 2007 Banff schema were applied, and current classification no longer requires positive C4d staining or detection of DSA 18 …”

“…Outcomes of immunosuppression reduction strategies during BKV treatment have been extensively studied 8,10,21–24 . In patients with BKV, tacrolimus reduction by ≥20% within 1 month of BKV diagnosis was recently associated with acute rejection rates of 34.2% compared to 7.9% in patients with less aggressive modifications ( P = .008) 16 .…”

“…Accumulating data suggest that BKV and BKVN are associated with the development of de novo donor‐specific antibodies (DSA) as well as acute rejection 6–12 . In biopsy series documenting the histologic evolution of definite and/or presumptive BKVN, approximately 40% of graft losses were compounded by rejection and Drachenberg et al reported that rejection increased the risk of graft loss by fourfold 6,7 .…”

Intravenous immunoglobulin as a preventive strategy against BK virus viremia and BKV-associated nephropathy in kidney transplant recipients—Results from a proof-of-concept study

“…Moreover, it is associated with an increased risk of developing donor-specific antibodies (DSA) and acute rejection. [10][11][12][13] In this scenario, novel strategies for preventing the deleterious effects of BKV are eagerly awaited.…”

“…Unfortunately, this approach proves successful only in 50%‐80% of cases 9 and does not eliminate the potential evolution to BKVAN. Moreover, it is associated with an increased risk of developing donor‐specific antibodies (DSA) and acute rejection 10‐13 . In this scenario, novel strategies for preventing the deleterious effects of BKV are eagerly awaited.…”