Leflunomide efficacy and pharmacodynamics for the treatment of BK viral infection

Clinical Journal of the American Society of Nephrology

Volumn 7, Issue 6, 2012, Pages 1003-1009

  Krisl, Jill C ^a   Taber, David J ^a   Pilch, Nicole ^a   Chavin, Kenneth ^b   Bratton, Charles ^b   Thomas, Beje ^a   McGillicuddy, John ^b   Baliga, Prabhakar ^b  

^a MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

^b MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DRUG METABOLITE; LEFLUNOMIDE; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; TERIFLUNOMIDE;

ADULT; ANEMIA; ARTICLE; BK VIRUS; BK VIRUS INFECTION; CONTROLLED STUDY; CORRELATIONAL STUDY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG EFFICACY; DRUG MONITORING; DRUG WITHDRAWAL; FEMALE; HUMAN; KIDNEY DISEASE; LEUKOPENIA; LIVER TOXICITY; LONGITUDINAL STUDY; MAJOR CLINICAL STUDY; MALE; PATIENT IDENTIFICATION; PHARMACODYNAMICS; POLYMERASE CHAIN REACTION; RETROSPECTIVE STUDY; THROMBOCYTOPENIA; VIREMIA; VIRUS LOAD;

ADULT; ANILINE COMPOUNDS; ANTIVIRAL AGENTS; BIOTRANSFORMATION; BK VIRUS; CHI-SQUARE DISTRIBUTION; DRUG MONITORING; FEMALE; HUMANS; HYDROXYBUTYRATES; IMMUNOSUPPRESSIVE AGENTS; ISOXAZOLES; KIDNEY TRANSPLANTATION; MALE; MIDDLE AGED; MULTIVARIATE ANALYSIS; MYCOPHENOLIC ACID; POLYMERASE CHAIN REACTION; POLYOMAVIRUS INFECTIONS; PROPORTIONAL HAZARDS MODELS; RETROSPECTIVE STUDIES; SOUTH CAROLINA; TREATMENT OUTCOME; TUMOR VIRUS INFECTIONS; VIRAL LOAD;

EID: 84862166878     PISSN: 15559041     EISSN: 1555905X     Source Type: Journal    
DOI: 10.2215/CJN.12531211     Document Type: Article

References (27)

1. Blanckaert K, De Vriese AS: Current recommendations for diagnosis and management of polyoma BK virus nephropathy in renal transplant recipients. NephrolDial Transplant 21: 3364-3367, 2006
2. Wu JK, Harris MT: Use of leflunomide in the treatment of polyomavirus BK-associated nephropathy. Ann Pharmacother 42: 1679-1685, 2008
3. Hirsch HH, Randhawa P; AST Infectious Diseases Community of Practice: BK virus in solid organ transplant recipients. Am J Transplant 9[Suppl 4]: S136-S146, 2009
4. Hilton R, Tong CYW: Antiviral therapy for polyomavirus-associated nephropathy after renal transplantation. J Antimicrob Chemother 62: 855-859, 2008
5. Ramos E, Drachenberg CB, Wali R, Hirsch HH: The decade of polyomavirus BK-associated nephropathy: State of affairs. Transplantation 87: 621-630, 2009
6. Johnston O, Jaswal D, Gill JS, Doucette S, Fergusson DA, Knoll GA: Treatment of polyomavirus infection in kidney transplant recipients: A systematic review. Transplantation 89: 1057-1070, 2010
7. Josephson MA, Gillen D, Javaid B, Kadambi P, Meehan S, Foster P, Harland R, Thistlethwaite RJ, Garfinkel M, Atwood W, Jordan J, Sadhu M, Millis MJ, Williams J: Treatment of renal allograft polyoma BK virus infection with leflunomide. Transplantation 81: 704-710, 2006
8. Ramos E, Drachenberg CB, Papadimitriou JC, Hamze O, Fink JC, Klassen DK, Drachenberg RC, Wiland A, Wali R, Cangro CB, Schweitzer E, Bartlett ST, Weir MR: Clinical course of polyoma virus nephropathy in 67 renal transplant patients. J AmSoc Nephrol 13: 2145-2151, 2002
9. Randhawa PS, Finkelstein S, Scantlebury V, Shapiro R, Vivas C, Jordan M, Picken MM, Demetris AJ: Human polyoma virusassociated interstitial nephritis in the allograft kidney. Transplantation 67: 103-109, 1999
10. Saad ER, Bresnahan BA, Cohen EP, Lu N, Orentas RJ, Vasudev B, Hariharan S: Successful treatment of BK viremia using reduction in immunosuppressionwithout antiviral therapy. Transplantation 85: 850-854, 2008
11. Cannon RM, Ouseph R, Jones CM, Hughes MG, Eng M, Marvin MR: BK viral disease in renal transplantation. Curr Opin Organ Transplant 16: 576-579, 2011
12. Leca N: Leflunomide use in renal transplantation. Curr Opin Organ Transplant 14: 370-374, 2009
13. Leca N, Muczynski KA, Jefferson JA, de Boer IH, Kowalewska J, Kendrick EA, Pichler R, Davis CL: Higher levels of leflunomide are associatedwith hemolysis and are not superior to lower levels for BK virus clearance in renal transplant patients. Clin J Am Soc Nephrol 3: 829-835, 2008
14. Prakash A, Jarvis B: Leflunomide: A review of its use in active rheumatoid arthritis. Drugs 58: 1137-1164, 1999
15. Rozman B: Clinical pharmacokinetics of leflunomide. Clin Pharmacokinet 41: 421-430, 2002
16. Cherwinski HM, Cohn RG, Cheung P, Webster DJ, Xu YZ, Caulfield JP, Young JM, Nakano G, Ransom JT: The immunosuppressant leflunomide inhibits lymphocyte proliferation by inhibiting pyrimidine biosynthesis. J Pharmacol Exp Ther 275: 1043-1049, 1995
17. Farasati NA, Shapiro R, Vats A, Randhawa P: Effect of leflunomide and cidofovir on replication of BK virus in an in vitro culture system. Transplantation 79: 116-118, 2005
18. Faguer S, Hirsch HH, Kamar N, Guilbeau-Frugier C, Ribes D, Guitard J, Esposito L, Cointault O, Modesto A, Lavit M, Mengelle C, Rostaing L: Leflunomide treatment for polyomavirus BK-associated nephropathy after kidney transplantation. Transpl Int 20: 962-969, 2007
19. Basse G, Mengelle C, Kamar N, Guitard J, Ribes D, Esposito L, Rostaing L: Prospective evaluation of BK virus DNAemia in renal transplant patients and their transplant outcome. Transplant Proc 39: 84-87, 2007
20. Williams JW, Javaid B, Kadambi PV, Gillen D, Harland R, Thistlewaite JR, Garfinkel M, Foster P, Atwood W, Millis JM, Meehan SM, Josephson MA: Leflunomide for polyomavirus type BK nephropathy. N Engl J Med 352: 1157-1158, 2005
21. Williams JW, Mital D, Chong A, Kottayil A, Millis M, Longstreth J, Huang W, Brady L, Jensik S: Experiences with leflunomide in solid organ transplantation. Transplantation 73: 358-366, 2002
22. Guasch A, Roy-Chaudhury P, Woodle ES, Fitzsimmons W, Holman J, First MR; FK778 BK Nephropathy Study Group: Assessment of efficacy and safety of FK778 in comparison with standard care in renal transplant recipients with untreated BK nephropathy. Transplantation 90: 891-897, 2010
23. Davis JP, Cain GA, Pitts WJ, Magolda RL, Copeland RA: The immunosuppressive metabolite of leflunomide is a potent inhibitor of human dihydroorotate dehydrogenase. Biochemistry 35: 1270-1273, 1996
24. Manna SK, Aggarwal BB: Immunosuppressive leflunomide metabolite (A77 1726) blocks TNF-dependent nuclear factor-kappa B activation and gene expression. J Immunol 162: 2095-2102, 1999
25. Teschner S, Gerke P, Geyer M, Wilpert J, Krumme B, Benzing T, Walz G: Leflunomide therapy for polyomavirus-induced allograft nephropathy: Efficient BK virus elimination without increased risk of rejection. Transplant Proc 41: 2533-2538, 2009
26. Alméras C, Foulongne V, Garrigue V, Szwarc I, Vetromile F, Segondy M, Mourad G: Does reduction in immunosuppression in viremic patients prevent BK virus nephropathy in de novo renal transplant recipients? A prospective study. Transplantation 85: 1099-1104, 2008
27. Schold JD, Rehman S, Kayle LK, Magliocca J, Srinivas TR, Meier-Kriesche HU: Treatment for BK virus: incidence, risk factors and outcomes for kidney transplant recipients in the United States. Transpl Int 22: 626-634, 2009