Treatment of renal allograft polyoma BK virus infection with leflunomide.
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.
Josephson
Michelle A
MA
Section of Nephrology, University of Chicago, Chicago, IL 60637, USA.
Gillen
Daniel
D
Javaid
Basit
B
Kadambi
Pradeep
P
Meehan
Shane
S
Foster
Preston
P
Harland
Robert
R
Thistlethwaite
Richard J
RJ
Garfinkel
Marc
M
Atwood
Walter
W
Jordan
Joslynn
J
Sadhu
Molly
M
Millis
Michael J
MJ
Williams
James
J
D000814:Aniline Compounds / Q000494:pharmacology; D001739:BK Virus / Q000187:drug effects* / Q000302:isolation & purification; D001769:Blood / Q000821:virology; D002478:Cells, Cultured; D003404:Creatinine / Q000097:blood; D003437:Crotonates; D005260:Female; D006801:Humans; D006885:Hydroxybutyrates / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D007555:Isoxazoles / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D007668:Kidney / Q000502:physiology / Q000503:physiopathology / Q000821:virology; D016030:Kidney Transplantation; D000077339:Leflunomide; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D027601:Polyomavirus Infections / Q000188:drug therapy*; D051437:Renal Insufficiency / Q000188:drug therapy* / Q000821:virology*; D016559:Tacrolimus / Q000627:therapeutic use; D014052:Toluidines; D014556:Urine / Q000821:virology; D014779:Virus Replication / Q000187:drug effects
D000814:Aniline Compounds; D003437:Crotonates; D006885:Hydroxybutyrates; D007166:Immunosuppressive Agents; D007555:Isoxazoles; D009570:Nitriles; D014052:Toluidines; C527525:teriflunomide; D003404:Creatinine; D000077339:Leflunomide; D016559:Tacrolimus