Treatment of renal allograft polyoma BK virus infection with leflunomide

Transplantation. 2006 Mar 15;81(5):704-10. doi: 10.1097/01.tp.0000181149.76113.50.

Abstract

Background: Polyoma BK virus produces an aggressively destructive nephropathy in approximately 3% to 8% of renal allografts, is associated with graft loss within one year in 35% to 67% of those infected and there is no therapy of proven efficacy. Leflunomide is an immune suppressive drug with anti viral activity in vitro and in animals.

Methods: We treated twenty-six patients with biopsy proven NK virus nephropathy (BKN) with either leflunomide alone (n=17) or leflunomide plus a course of cidofovir (n=9) and followed them for six to forty months. Leflunomide was dosed to a targeted blood level of active metabolite, A77 1726, of 50 microg/ml to 100 microg/ml (150 microM to 300 microM). Response to treatment was gauged by serial determinations of viral load in blood and urine (PCR), serum creatinine, and repeat allograft biopsy.

Results: In the 22 patients consistently sustaining the targeted blood levels of active drug, blood and urine viral load levels uniformly decreased over time (P<.001). Mean serum creatinine levels stabilized over the first six months of treatment, and with 12 months or more of follow-up in 16 patients the mean serum creatinine has not changed significantly from base line. Four patients who did not consistently have blood levels of active drug (A77 1726) above 40 microg/ml did not clear the virus until these levels were attained or cidofovir was added.

Conclusions: Leflunomide inhibits Polyoma virus replication in vitro and closely monitored leflunomide therapy with specifically targeted blood levels appears to be a safe and effective treatment for Polyoma BK nephropathy.

MeSH terms

  • Aniline Compounds / pharmacology
  • BK Virus / drug effects*
  • BK Virus / isolation & purification
  • Blood / virology
  • Cells, Cultured
  • Creatinine / blood
  • Female
  • Humans
  • Hydroxybutyrates / pharmacology
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / blood
  • Immunosuppressive Agents / therapeutic use*
  • Isoxazoles / adverse effects
  • Isoxazoles / blood
  • Isoxazoles / therapeutic use*
  • Kidney / physiology
  • Kidney / physiopathology
  • Kidney / virology
  • Kidney Transplantation*
  • Leflunomide
  • Male
  • Middle Aged
  • Polyomavirus Infections / drug therapy*
  • Renal Insufficiency / drug therapy*
  • Renal Insufficiency / virology*
  • Tacrolimus / therapeutic use
  • Urine / virology
  • Virus Replication / drug effects

Substances

  • Aniline Compounds
  • Hydroxybutyrates
  • Immunosuppressive Agents
  • Isoxazoles
  • teriflunomide
  • Creatinine
  • Leflunomide
  • Tacrolimus