Treatment of renal allograft polyoma BK virus infection with leflunomide

Michelle A. Josephson, Daniel Gillen, Basit Javaid, Pradeep Kadambi, Shane Meehan, Preston Foster, Robert Harland, Richard J. Thistlethwaite, Marc Garfinkel, Walter Atwood, Joslynn Jordan, Molly Sadhu, Michael J. Millis, James Williams

Research output: Contribution to journalArticlepeer-review

163 Scopus citations

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 μg/ml to 100 μg/ml (150 μM to 300 μM). 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 μg/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.

Original languageEnglish (US)
Pages (from-to)704-710
Number of pages7
JournalTransplantation
Volume81
Issue number5
DOIs
StatePublished - Mar 1 2006
Externally publishedYes

Keywords

  • Cidofovir
  • Kidney transplant
  • Leflunomide
  • Polyoma BK
  • Polyoma BK nephropathy

ASJC Scopus subject areas

  • Transplantation

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