Tacrolimus Dose Reduction as an Effective Therapeutic Approach to the Patients with Active BK Polyomavirus Replication and Nephrotoxicity

BK polyomavirus nephropathy (BKPyV-nephropathy) leads to functional failure of kidney grafts in the early post-transplant period. The intensity of immunosuppressive therapy plays a significant role in the activation of BK polyomavirus (BKPyV) replication. We prospectively evaluated 457 per-protocol biopsies of kidney grafts in a group of 161 newly transplanted patients within the 1 st year after surgery. The incidence of excessive immunosuppression was calculated using the Calcineurin Inhibitor Nephrotoxicity Score (CINS). In case of detection of toxicity and BKPyV replication, the dose of tacrolimus and/or mycophenolate was reduced and the effect on the inhibition of BKPyV activation and regression of toxic changes were compared. In parallel, we studied the effect of preemptive reduction of tacrolimus dose on the onset of BKPyV replication in case of isolated detections of toxicity. A concomitant dose reduction of tacrolimus and mycophenolate in patients with histological evidence of toxicity and significant BKPyV replication was associated with an early and significant decrease in the plasma BKPyV-DNAemia load compared to isolated mycophenolate reduction (P = 0.023), significant decrease in CINS (P = 0.001) and better functional parameters at the end of one-year follow-up (P = 0.024). Preemptive tacrolimus dose reduction in case of toxicity signs was associated with a lower incidence of BKPyV replication, without increasing the risk of acute rejection.