Polyoma BK virus-associated nephropathy in kidney-transplant patients: Effects of leflunomide on T-cell functions and disease outcome

Canivet, Cindy; Rostaing, Lionel; Galvani, Sylvain; Böhler, Torsten; Gandia, Peggy; Mengelle, Catherine; Guilbeau‐Frugier, Céline; Thomsen, Mögens; Salvayre, Robert; Negre-Salvayre, Anne; Kamar, Nassim

doi:10.1016/j.intimp.2009.05.004

Cited by 13 publications

(8 citation statements)

References 39 publications

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“…Preliminary clinical data from small studies demonstrated viral clearance and reduction of viral load in kidney transplant recipients with BKVN treated with leflunomide . However, a recent systematic review failed to identify any benefit of the addition of leflunomide on graft survival following development of BKVN .…”

Section: Resultsmentioning

confidence: 99%

Effect of maintenance immunosuppressive drugs on virus pathobiology: evidence and potential mechanisms

Brennan

Aguado

Potena

et al. 2012

Reviews in Medical Virology

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Recent evidence suggesting a potential anti-CMV effect of mTORis is of great interest to the transplant community. However, the concept of an immunosuppressant with antiviral properties is not new, with many accounts of the antiviral properties of several agents over the years. Despite these reports, to date, there has been little effort to collate the evidence into a fuller picture. This manuscript was developed to gather the evidence of antiviral activity of the agents that comprise a typical immunosuppressive regimen against viruses that commonly reactivate following transplant (HHV1 and 2, VZV, EBV, CMV and HHV6, 7, and 8, HCV, HBV, BKV, HIV, HPV, and parvovirus). Appropriate immunosuppressive regimens posttransplant that avoid acute rejection while reducing risk of viral reactivation are also reviewed. The existing literature was disparate in nature, although indicating a possible stimulatory effect of tacrolimus on BKV, potentiation of viral reactivation by steroids, and a potential advantage of mammalian target of rapamycin (mTOR) inhibition in several viral infections, including BKV, HPV, and several herpesviruses.

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Section: Resultsmentioning

confidence: 99%

Effect of maintenance immunosuppressive drugs on virus pathobiology: evidence and potential mechanisms

Brennan

Aguado

Potena

et al. 2012

Reviews in Medical Virology

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“…Leflunomide is an immunosuppressive drug approved for the treatment of rheumatoid arthritis, which has apparent antiviral activity . The drug is currently used as a substitute for mycophenolate mofetil in patients who are believed to be at risk of BKVAN .…”

Section: Discussionmentioning

confidence: 99%

Treatment of BK virus‐associated nephropathy with CMX001 after kidney transplantation in a young child

Reisman

Habib

McClure

et al. 2014

Pediatric Transplantation

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NC, with renal failure secondary to bilateral dysplastic kidneys, received an LRD renal transplant (tx) at 17 months of age. Her early post-tx course was complicated by persistently elevated blood polyoma BK virus DNA loads. A protocol biopsy at six months post-transplant revealed BKVAN. Blood viral loads did not respond to decreased immunosuppression or treatment with ciprofloxacin and leflunomide. Six months post-tx, her serum creatinine began to rise and we sought experimental therapy to prevent the loss of her graft. At seven months post-tx, with FDA approval under an eIND, the patient was started on a 36-wk course of treatment with the investigational drug. The patient is now more than 24 months after stopping treatment with CMX. BKV viral DNA loads remain at low, but still detectable levels. Urine viral loads have declined, but remain elevated. EBV DNA loads become undetectable. The patient's serum creatinine has declined back to a baseline of 0.5-0.7 mg/dL and has been stable for two yr. Renal function was preserved in association with the use of CMX001 to treat BKV nephropathy in a young pediatric kidney transplant recipient. There were no serious adverse events associated with the use of CMX001. This novel medication may be of value in the treatment of BKVAN in pediatric renal transplant recipients.

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“…Leflunomide has been used as second-line therapy in refractory infection after reducing maintenance immunosuppression, and has been used alone or in combination with other drugs. 31,[57][58][59][60][61] In vitro studies show that leflunomide at 10 μg/mL can reduce viral load by inhibiting host cells-BK viral replication, late protein expression, virion assembly and release associated with visible disruption of the nuclear replication architecture. Both host cell and antiviral effects were largely reversed by uridine addition, implicating pyrimidine depletion as the major mechanism of leflunomide.…”

Section: Polyomavirusmentioning

confidence: 99%

Leflunomide: Traditional immunosuppressant with concurrent antiviral effects

et al. 2022

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Leflunomide is a classic disease‐modifying anti‐rheumatic drug that is widely used to treat autoimmune diseases. Studies also show its antiviral effects in in vitro and/or in vivo experiments. Considering glucocorticoids, immunosuppressants and newly emerged antibodies commonly used in autoimmune diseases and autoinflammatory disorders bring risk of infection such as viral infection, leflunomide with combination of anti‐viral and immunosuppressive features to maintain the balance between infection and anti‐inflammation are attractive. Here we summarize the actions and mechanisms of leflunomide in immunoregulatory and antiviral effects.

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Polyoma BK virus-associated nephropathy in kidney-transplant patients: Effects of leflunomide on T-cell functions and disease outcome

Cited by 13 publications

References 39 publications

Effect of maintenance immunosuppressive drugs on virus pathobiology: evidence and potential mechanisms

Effect of maintenance immunosuppressive drugs on virus pathobiology: evidence and potential mechanisms

Treatment of BK virus‐associated nephropathy with CMX001 after kidney transplantation in a young child

Leflunomide: Traditional immunosuppressant with concurrent antiviral effects

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