Incidence and outcome of BK polyomavirus infection in a multicenter randomized controlled trial with renal transplant patients receiving cyclosporine‐, mycophenolate sodium‐, or everolimus‐based low‐dose immunosuppressive therapy

• Published in: Transplant infectious disease 2017-06, Vol.19 (3), p.n/a
• Main Authors: Doesum, Willem B., Gard, Lilli, Bemelman, Frederike J., Fijter, Johan W., Homan van der Heide, Jaap J., Niesters, Hubert G., Son, Willem J., Stegeman, Coen A., Groen, Henk, Riezebos‐Brilman, Annelies, Sanders, Jan Stephan F.
• Format: Article
• Language: English
• Subjects: Adult; BK Virus - isolation & purification; BK virus nephropathy; Clinical trials; cyclosporine; Cyclosporins; Data analysis; Data processing; Drug Therapy, Combination - adverse effects; Drug Therapy, Combination - methods; everolimus; Female; Health risk assessment; Humans; Immunosuppression; Immunosuppression - adverse effects; Immunosuppression - methods; Immunosuppressive agents; Immunosuppressive Agents - therapeutic use; Incidence; Infections; Kidney Failure, Chronic - surgery; Kidney transplantation; Kidney Transplantation - adverse effects; Male; Middle Aged; mycophenolate sodium; Mycophenolic acid; Nephropathy; Patients; polyomavirus; Polyomavirus Infections - blood; Polyomavirus Infections - epidemiology; Polyomavirus Infections - urine; Polyomavirus Infections - virology; Prednisolone; Prospective Studies; renal transplantation; Replication; Sodium; Therapy; Transplant Recipients; Tumor Virus Infections - blood; Tumor Virus Infections - epidemiology; Tumor Virus Infections - urine; Tumor Virus Infections - virology; Viral Load - drug effects; Viremia; Viremia - epidemiology; Viremia - urine; Viruria; Viruses
• ISSN: 1398-2273; 1399-3062
• DOI: 10.1111/tid.12687

Background It remains unclear whether overall degree of immunosuppression or specific effects of individual immunosuppressive agents are causal for increased occurrence of BK polyomavirus (BKPyV) infection in renal transplant recipients (RTR). Methods A prospective, multicenter, open‐label randomized controlled trial in 361 de novo RTR was performed. A total of 224 RTR were randomized at 6 months into three treatment groups with dual therapy consisting of prednisolone (Pred) plus either cyclosporine (CsA), mycophenolate sodium (MPS), or everolimus (EVL). Primary outcomes were incidence of BK viruria, BK viremia, and BKPyV‐associated nephropathy (BKVAN). Results From 6 months, incidence of BK viruria in the MPS group (43.6%) was significantly higher than in the other groups (CsA: 16.9%, EVL: 19.8%) (P=.003). BKVAN was diagnosed in 3 patients, all treated with MPS (7.8%, P=.001). Longitudinal data analysis showed a lower BKPyV load and a significantly faster clearance of BK viruria in the CsA group compared to the MPS group (P=.03). Conclusions Treatment with MPS was associated with an increased incidence of BK viruria. Dual immunosuppressive therapy with CsA and Pred was associated with the lowest rate of BKPyV replication and the fastest clearance of the virus.