Development of de novo donor‐specific antibodies in renal transplant recipients with BK viremia managed with immunosuppression reduction

Abstract

Background: Reduction of immunosuppression (IS) upon detection of Polyomavirus (BK) viremia is widely used to prevent BK virus nephropathy. This retrospective casecontrol study assesses the frequency of de novo donor-specific antibodies (dnDSA) in renal transplant recipients with IS modulation due to BK viremia and the associated risk of antibody mediated rejection. Methods: Our cohort included recipients of kidney transplantation between 2007 and 2017 with clinical, HLA antibody, and biopsy data. BK positivity was defined as viremia >10 000 c/ml or biopsy proven BK nephropathy. A total of 190 BK cases matched our inclusion criteria, each case was matched with two controls based on gender, donor type, and transplant within 1 year (N = 396).Results: Despite lower number of HLA antigen mismatches (mean = 3.5 vs. 4.4, p < .001), dnDSA rates were higher in BK cases than in control group (22.1% vs. 13.9%, p = .02), with the majority detected following IS reduction for BK infection, and arising earlier posttransplant compared with no BK infection (294d vs. 434d, p < .001). Antibody mediated rejection rates were similar between cases and controls (8.9% and 8.3%, respectively), but rejection was more likely to occur earlier posttransplant in the BK cases (354d vs. 602d, p = .03). Conclusion:Our data suggest a link between IS reduction and the generation of dnDSA and/or rejection, supporting close monitoring for DSA in patients with reduced IS due to BK infection given their increased risk to develop dnDSA.

Polyomavirus nephropathy: diagnosis, histologic features, and differentiation from acute rejection

“…In a study by Gras et al [15], acute rejection was found in 13.8% of patients with BKVN at a median of 16 months after infection compared with 3% of matched controls (P=0.003), with a significantly higher level of donor-specific antibodies (DSA) in the BKVN patients. Other investigators also have noted a higher level of DSA following BKVN, and up to 45% of rejection episodes are antibody-mediated or mixed rejection [62,[95][96][97][98].…”

BK polyomavirus DNAemia, allograft rejection, and de novo donor‐specific antibodies after lowering target tacrolimus levels in pediatric kidney transplant recipients

“…As previously described in the literature, rejection and dnDSA could be consequences of immunosuppression reduction after the diagnosis of BKV DNAemia. 7,23,24 On the other hand, BKV reactivation could follow treatment for acute rejection. 25 Therefore, we wanted to study the association between these events, which have profound impact on post-KT immunosuppression management.…”

“…Close monitoring of plasma BKV PCR and graft function and timely reduction of the overall level of immunosuppression when patients develop BKV DNAemia are suggested in order to prevent BKVAN 6 . However, reduction of immunosuppression, especially in the early post‐KT phase, could increase the risk of allosensitization, which might result in clinical or subclinical rejection 7–9 . Therefore, as clinicians try to achieve the fine balance between BKVAN and rejection, patients might require more clinic visits, laboratory tests, venipunctures, adjustment of immunosuppressive medications, and allograft biopsies, all of which add to the complexity and cost of post‐KT care.…”

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

“…4,5 BKVN outcomes are heterogeneous with reported rates of acute rejection in 10%-40% of cases and graft loss ranging from <10% to >80%. 6,7 This heterogeneity is further confounded by differences in modality and frequency of BKV screening practices due to limited evidence resulting in differential guideline recommendations by American Society of Transplantation Infectious Diseases Community of Practice (AST-IDCOP) and Kidney Disease Improving Global Outcomes (KDIGO). 8,9 Immunosuppression reduction is foundational to BKV management, yet lack of randomized controlled trials has resulted in no internationally accepted approach regarding type, order, intensity, and duration of immunosuppression reduction.…”

“…Kidney transplant recipients develop viruria in 30%–60%, viremia in 10%–30%, and biopsy‐proven BKV nephropathy (BKVN) in 5%–10% 4,5 . BKVN outcomes are heterogeneous with reported rates of acute rejection in 10%–40% of cases and graft loss ranging from <10% to >80% 6,7 . This heterogeneity is further confounded by differences in modality and frequency of BKV screening practices due to limited evidence resulting in differential guideline recommendations by American Society of Transplantation Infectious Diseases Community of Practice (AST‐IDCOP) and Kidney Disease Improving Global Outcomes (KDIGO) 8,9 …”