title: 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.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Willem B
authors.initials: WB
authors.lastname: van Doesum
authors.affiliation: Department of Clinical Virology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Lilli
authors.initials: L
authors.lastname: Gard
authors.affiliation: Renal Transplant Unit, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Frederike J
authors.initials: FJ
authors.lastname: Bemelman
authors.affiliation: Renal Transplant Unit, Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Johan W
authors.initials: JW
authors.lastname: de Fijter
authors.affiliation: Renal Transplant Unit, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jaap J
authors.initials: JJ
authors.lastname: Homan van der Heide
authors.affiliation: Department of Clinical Virology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Hubert G
authors.initials: HG
authors.lastname: Niesters
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Willem J
authors.initials: WJ
authors.lastname: van Son
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Coen A
authors.initials: CA
authors.lastname: Stegeman
authors.affiliation: Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Henk
authors.initials: H
authors.lastname: Groen
authors.affiliation: Department of Clinical Virology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Annelies
authors.initials: A
authors.lastname: Riezebos-Brilman
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Jan Stephan F
authors.initials: JSF
authors.lastname: Sanders
mesh_terms: D000328:Adult; D001739:BK Virus / Q000302:isolation & purification; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects* / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015994:Incidence; D007676:Kidney Failure, Chronic / Q000601:surgery*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D027601:Polyomavirus Infections / Q000097:blood / Q000453:epidemiology* / Q000652:urine / Q000821:virology; D011446:Prospective Studies; D066027:Transplant Recipients; D014412:Tumor Virus Infections / Q000097:blood / Q000453:epidemiology* / Q000652:urine / Q000821:virology; D019562:Viral Load / Q000187:drug effects; D014766:Viremia / Q000453:epidemiology / Q000652:urine
chemical_list: D007166:Immunosuppressive Agents
keywords: BK virus nephropathy; cyclosporine; everolimus; immunosuppression; mycophenolate sodium; polyomavirus; renal transplantation