Polyoma BK virus-associated nephropathy in kidney-transplant patients: Effects of leflunomide on T-cell functions and disease outcome.
BACKGROUND
In kidney-transplant recipients, leflunomide has been shown to be efficient for treating polyomavirus BK virus-associated-nephropathy (PVAN). However, it is unknown whether the beneficial effect of leflunomide is related to it having a lower immunosuppressive effect than mycophenolate mofetil (MMF), or to its anti-viral activity. The aim of this study was to assess i) T-cell functions before and after conversion from MMF to leflunomide in kidney-transplant patients with PVAN, and ii) effects of leflunomide on PVAN outcome.


METHODS
Twelve patients were enrolled in this study. At PVAN diagnosis, MMF was replaced by leflunomide. Other immunosuppressive drug doses and levels were maintained unchanged. T-cell functions, i.e., intralymphocyte cytokine expression (IL-2 and TNF-alpha), T-cell activation [i.e., transferrin receptor (CD71) and interleukin (IL)-2 alpha-chain (CD25) expression], and T-cell proliferation were measured using a flow-cytometry whole-blood assay before and at one month after conversion.


RESULTS
Despite a slight decrease in tacrolimus trough levels, no significant change in T-cell-function biomarkers was observed after conversion. After a follow-up of 6 (4-30) months, five patients were cleared of the virus, and decreased viral load was observed in four patients. Only one patient suffered a graft loss. No difference in immunological parameters was observed between patients who were cleared or not of BKV.


CONCLUSIONS
Results of this pilot study suggest that the potential benefits of leflunomide to treat PVAN in kidney-transplant patients is not related to reduced immunosuppression induced by replacing MMF by leflunomide. Virological studies are required to determine the anti-BKV effect of leflunomide.
Canivet
Cindy
C
INSERM U/MR, Toulouse, France.
Rostaing
Lionel
L
Galvani
Sylvain
S
Böhler
Torsten
T
Gandia
Peggy
P
Mengelle
Catherine
C
Guilbeau-Frugier
Céline
C
Thomsen
Mogens
M
Salvayre
Robert
R
Negre-Salvayre
Anne
A
Kamar
Nassim
N
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D001739:BK Virus / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000150:complications / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007555:Isoxazoles / Q000008:administration & dosage; D007668:Kidney / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000821:virology; D016030:Kidney Transplantation; D000077339:Leflunomide; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D009393:Nephritis / Q000209:etiology; D027601:Polyomavirus Infections / Q000150:complications / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D011990:Receptors, Transferrin / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D015703:Antigens, CD; C068126:CD71 antigen; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D007555:Isoxazoles; D011990:Receptors, Transferrin; D014409:Tumor Necrosis Factor-alpha; D000077339:Leflunomide; D009173:Mycophenolic Acid