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Tacrolimus + leflunomide is a combination therapy being evaluated for the treatment of BK virus (BKV) infection in kidney transplant recipients. Tacrolimus is a calcineurin inhibitor that serves as a cornerstone of post-transplant immunosuppression by preventing T-lymphocyte activation. Leflunomide is an immunomodulatory agent that inhibits dihydroorotate dehydrogenase (DHODH), an enzyme essential for de novo pyrimidine synthesis. In addition to its immunosuppressive properties, leflunomide has demonstrated antiviral activity against the BK polyomavirus, likely by interfering with viral DNA replication or virion assembly. This specific combination, often involving a reduction in the tacrolimus dose to lower the overall immunosuppressive burden, is being studied by King Chulalongkorn Memorial Hospital as a strategy to clear BKV viremia and prevent BKV-associated nephropathy (BKVAN) while maintaining graft protection.
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