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

Transpl Infect Dis. 2017 Jun;19(3). doi: 10.1111/tid.12687. Epub 2017 May 4.

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.

Keywords: BK virus nephropathy; cyclosporine; everolimus; immunosuppression; mycophenolate sodium; polyomavirus; renal transplantation.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • BK Virus / isolation & purification
  • Drug Therapy, Combination / adverse effects
  • Drug Therapy, Combination / methods
  • Female
  • Humans
  • Immunosuppression Therapy / adverse effects*
  • Immunosuppression Therapy / methods
  • Immunosuppressive Agents / therapeutic use*
  • Incidence
  • Kidney Failure, Chronic / surgery*
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Polyomavirus Infections / blood
  • Polyomavirus Infections / epidemiology*
  • Polyomavirus Infections / urine
  • Polyomavirus Infections / virology
  • Prospective Studies
  • Transplant Recipients
  • Tumor Virus Infections / blood
  • Tumor Virus Infections / epidemiology*
  • Tumor Virus Infections / urine
  • Tumor Virus Infections / virology
  • Viral Load / drug effects
  • Viremia / epidemiology
  • Viremia / urine

Substances

  • Immunosuppressive Agents