AbstractBackgroundReduction of immunosuppression (IS) upon detection of Polyomavirus (BK) viremia is widely used to prevent BK virus nephropathy. This retrospective case‐control 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.MethodsOur 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).ResultsDespite 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).ConclusionOur 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. image