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

Abstract

Backgrounds: Effective management of BK viremia (BKPyV-DNAemia) in kidney transplant recipients (KTRs) involves regular monitoring and adjustment of immunosuppression. With this strategy, the majority of patients will clear BK or have ongoing, but non-significant, low-level BKPyV-DNAemia. However, despite adjustments, some will develop more severe sequelae of BK including BKPyV-DNAemia >5 log 10 copies/mL and BK nephropathy, and others may develop de novo DSA (dnDSA) or acute rejection (AR).Methods: This was a single-center study of KTRs transplanted at the University of Wisconsin-Madison between 01/01/2015 and 12/31/2017. In this study, we sought to elucidate characteristics associated with the progression of BKPyV-DNAemia to unfavorable outcomes after decreasing immunosuppressive medications for the management of BK viremia as described in consensus guidelines.Results: A total of 224 KTRs fulfilled our selection criteria; 118 (53%) resolved or had persistent low DNAemia, 64 (28%) had severe BK/nephropathy, and 42 (19%) developed dnDSA or AR.

Risk factors and outcomes of BK viremia among deceased donor kidney transplant recipients based on donor characteristics

“…Protocol biopsies are performed on all patients with dnDSA, and also on patients with pre-transplant DSA at 3 and 12 months post-transplant, as previously described. 2 Biopsies are only performed on KTRs with BK viremia if they are experiencing unstable graft function.…”

“…However, this virus does not cause disease in immunocompetent individuals due to functional T-cell immunity. [1][2][3][4] In kidney transplant recipients (KTR), infection with BKV can be progressive, proceeding from viruria to viremia to nephropathy. 5,6 BK viremia is important, given the association with BK nephropathy (BKN), impaired graft function, and premature graft failure.…”

“…8,[10][11][12] Some of these patients will progress to BKN, but most will clear their infection after the reduction of their immunosuppressive therapy. 2 Immunosuppressive intensity is currently the only widely accepted risk factor for BK viremia, [13][14][15] and while other risk factors have been reported, these are mostly theoretical and without robust literature support. Evidence suggests BK viremia is predominantly donor-derived rather than reactivation of the recipient latent infection.…”

Role of Virus-Specific T Cell Therapy for Cytomegalovirus and BK Infections in Kidney Transplant Recipients

“…This presents a real challenge in post-transplant management, because immunosuppression is indicated for the prevention of graft rejection (28). In our institutional experience, stepwise immunosuppression reduction after diagnosis of BK viremia was effective in inducing resolution of viremia only in around half of patients; approximately one quarter of the remaining progressed to detrimental outcomes of either severe BK viremia or BKN, and the remaining one quarter developed de novo donor-specific antibody against HLA or experienced acute rejection (34).…”

Association of BKV viremia and nephropathy with adverse alloimmune outcomes in kidney transplant recipients

“…13,14 Furthermore, increased HLA MM also confers an increased risk for developing dnDSA or ABMR after immunosuppression reduction to treat BKV. 15 A nuanced understanding of alloimmune risk to the allograft following BKV infection and immunosuppression reduction is lacking.…”