Increasing net immunosuppression after BK polyoma virus infection

Abstract

Background Reducing immunosuppression can effectively treat BK viremia (BKV) and BK nephropathy, but has been associated with increased risks for acute rejection and development of donor‐specific antibodies (DSA). To date there have been no systematic evaluations of re‐escalating immunosuppression in transplant patients with resolving BKV. Importantly, the safety of this approach and impact on graft survival is unclear. Methods We performed a single‐center retrospective review of kidney transplant recipients between July 2011 and June 2013 who had immunosuppression reduction after developing BKV (plasma PCR ≥ 1000 copies/ml). Changes in immunosuppression and patient outcomes were tracked until occurrence of a complication event: biopsy‐proven acute rejection (BPAR), detection of de novo DSA, or recurrent BKV. Patients were grouped according to whether or not net immunosuppression was eventually increased. Results Out of 88 patients with BKV, 44 (50%) had net immunosuppression increased while the other 44 did not. Duration of viremia, peak viremia, induction, and sensitization status were similar between the two groups. In a Kaplan‐Meier analysis, increasing immunosuppression was associated with less BPAR (P = .001) and a trend toward less de novo DSA development (P = .06). Death‐censored graft survival (P = .27) was not different between the two groups. In the net immunosuppression increase group, recurrent BKV occurred in 22.7% without any BKV‐related graft losses. Conclusion These findings support potential benefits of increasing immunosuppression in patients with low‐level or resolved BKV, but prospective trials are needed to better understand such an approach.

Impact of antimetabolite discontinuation following cytomegalovirus or BK polyoma virus infection in kidney transplant recipients

“…Incidence of BPAR was 21.6%, with both a higher rate and shorter time to rejection in patients who did not undergo re-escalation. 9 The authors suggest that increasing net immunosuppression after BK viremia may be protective in preventing acute rejection in select patients without an unacceptably high risk of recurrent viremia. 9 Similarly, a pilot study of 36 kidney transplant recipients assessed the impact of a stepwise dose-escalation of mycophenolate followed by tacrolimus to standard pre-viremia doses following resolution of BK viremia.…”

“…9 The authors suggest that increasing net immunosuppression after BK viremia may be protective in preventing acute rejection in select patients without an unacceptably high risk of recurrent viremia. 9 Similarly, a pilot study of 36 kidney transplant recipients assessed the impact of a stepwise dose-escalation of mycophenolate followed by tacrolimus to standard pre-viremia doses following resolution of BK viremia. 10 This strategy appeared to be well-tolerated, with only one patient developing recurrence of low level viremia.…”

“…Furthermore, immunosuppression management after resolution of CMV or BKV DNAemia is not addressed in current guidelines and various strategies have been evaluated in a limited number of studies, with heterogenous patient populations largely focused on management following BKV infection 9,10 . Re‐escalation of immunosuppression may offer potential benefit in preventing subsequent rejection episodes in patients who achieve viral DNAemia clearance 9,10 …”

“…Furthermore, immunosuppression management after resolution of CMV or BKV DNAemia is not addressed in current guidelines and various strategies have been evaluated in a limited number of studies, with heterogenous patient populations largely focused on management following BKV infection. 9,10 Re-escalation of immunosuppression may offer potential benefit in preventing subsequent rejection episodes in patients who achieve viral DNAemia clearance. 9,10 The purpose of this study was two-fold; to describe episodes of acute rejection following antimetabolite discontinuation after detection of CMV or BKV DNAemia in kidney transplant recipients maintained on triple-drug immunosuppression at the time of DNAemia detection and identify risk factors for rejection in this population.…”

Risk factors for progression from low level BK dnaemia to unfavorable outcomes after BK management via immunosuppressive reduction

“…nephropathy to dnDSA and/or rejection was not uncommon in our population, as has been stressed in a recent report from another academic transplant center. 19 Having BKPyVAN and the features of AMR as indicated by microvascular inflammation along with poor graft function (with serum creatinine >2 mg/dL) at presentation are strongly associated with graft failure. 20 Clinical manifestations of BKPyV develop in stages progressing from viruria to BKPyV-DNAemia and eventually into BKPyVAN.…”