Immunosuppression, BK polyomavirus infections, and BK polyomavirus-specific T cells after pediatric kidney transplantation.

Abstract

After kidney transplantation, immunosuppressive therapy increases risk of BK polyomavirus-associated nephropathy (BKPyVAN). Outcomes of BKPyV viremia are various and prognostic markers are missing. The impact of different immunosuppressive regimens on BKPyV infections is currently under discussion. We analyzed immunosuppressive therapy and BKPyV-specific cellular immunity to distinguish patients at risk of BKPyVAN from those with self-limiting viremia for purposes of risk-stratified BKPyV management. In a retrospective analysis, 46 pediatric kidney recipients with BKPyV viremia were analyzed with regard to duration of BKPyV viremia and immunosuppressive therapy; in addition, in 37/46 patients, BKPyV-specific CD4 and CD8 T cells were measured. Nine patients showed persistent BKPyV viremia and BKPyVAN, and required therapeutic intervention, while 37 patients had asymptomatic, self-limiting viremia. At onset of viremia, 78% of patients with persistent viremia and BKPyVAN were treated with tacrolimus, whereas tacrolimus therapy was significantly less frequent in patients with self-limiting viremia (14%). The majority of patients with transient, self-limiting viremia received cyclosporine A (81%) and/or mTOR inhibitors (81%). Patients with persistent BKPyV viremia and BKPyVAN showed lack of BKPyV-specific CD4 and CD8 T cells (6/6), whereas the majority of patients with self-limiting viremia (27/31) had detectable BKPyV-specific CD4 and/or CD8 T cells ≥ 0.5 cells/μl (p < 0.001). These results indicate that tacrolimus enhances risk of BKPyVAN with need of therapeutic intervention, whereas under cyclosporine A and mTOR inhibitors, the majority of pediatric kidney recipients showed self-limiting viremia. In patients at risk of BKPyV infections, combination of cyclosporine A and mTOR inhibitor may be advantageous.