Reducing immunosuppression is the mainstay of treating BK polyomavirus (BKPyV) viraemia after kidney transplantation, but the best approach, efficacy and impact are undefined. We established a standard operating procedure (SOP) treating BKPyV viraemia based on first reducing calcineurin inhibitor (‘CNI first’). The aim of this study was to investigate long-term outcomes in 644 consecutive transplantations using this SOP.

Patients were monitored for active BKPyV infection by urinary decoy cells and, if positive, by BKPyV viraemia. In case of sustained BKPyV viraemia >1000 copies/mL, immunosuppression was reduced stepwise according to the SOP. Patients were classified as ‘no decoy cells’ [n = 432 (66%)], ‘decoy cells/no viraemia’ [n = 107 (17%)] and ‘viraemia’ [n = 105 (17%)].

At 6-years post-transplant, graft survival was ∼84%, the clinical rejection rate was ∼25% and they were not different among the three groups (P = 0.14; P = 0.91). The median estimated glomerular filtration rate at the last follow-up was similar (range 49–53 mL/min, P = 0.08). Of 105 viraemic patients, 101 (96%) cleared BKPyV viraemia. In 39% of patients, viraemia clearance followed a tacrolimus reduction. A reduction of mycophenolic acid was required in 43% and discontinuation in 3%. No short-term graft loss was directly attributable to BKPyV-associated nephropathy. After a median follow-up of 5 years after clearance of BKPyV viraemia, 11/101 patients (11%) developed clinical rejection: 7 (7%) T-cell-mediated rejection and 4 (4%) antibody-mediated rejection (ABMR).

Immunosuppression reduction based on ‘CNI first’ leads to similar long-term outcomes in patients with/without BKPyV viraemia and is associated with a low risk for ABMR after clearance of BKPyV viraemia. Randomized trials are needed to compare the risks and benefits of immunosuppression reduction strategies in kidney transplant patients with BKPyV viraemia.