title: Combination of Leflunomide and Everolimus for treatment of BK virus nephropathy.
abstract: BK nephropathy (BKN) is a common cause of graft dysfunction following kidney transplantation. Minimization of immunosuppressive therapy remains the first line of therapy, but this may lead to rejection and graft loss. In some cases, despite lowering immunosuppression, BK infection can persist, leading to chronic damage and kidney failure. Currently, there is no specific anti-BK viral therapy. Recent in vitro experiments have demonstrated a reduction in BK viral replication when infected cells are treated with the combination of Leflunomide and Everolimus. This study aims to explore the effect of this drugs combination on viral clearance and graft function in patients with persistent disease despite reduction in immunosuppression. We treated three patients with combination Leflunomide and Everolimus. Data on medical history, biochemical parameters and viral loads were collected. Significant improvement in viral loads was observed in two cases with resolution of viremia in another (Table 1). Two recipients had preserved allograft function. The remaining graft was lost because of combination of obstruction and BKN. No adverse reactions such as bone marrow toxicity were observed. Combination of Leflunomide and Everolimus is safe and should be considered as a rescue therapy in treatment of BKN, especially in those who fail to clear this infection despite reduction of immunosuppressive therapy.
authors.affiliation: Department of Nephrology, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia.
authors.forename: Juli
authors.initials: J
authors.lastname: Jaw
authors.affiliation: Department of Anatomical Pathology, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia.
authors.forename: Prue
authors.initials: P
authors.lastname: Hill
authors.affiliation: Department of Nephrology, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Goodman
mesh_terms: D000368:Aged; D001739:BK Virus / Q000187:drug effects* / Q000276:immunology; D057915:Drug Substitution; D004359:Drug Therapy, Combination; D000068338:Everolimus / Q000627:therapeutic use*; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007555:Isoxazoles / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000009:adverse effects*; D000077339:Leflunomide; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D027601:Polyomavirus Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D013997:Time Factors; D016896:Treatment Outcome; D014412:Tumor Virus Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D019562:Viral Load
chemical_list: D007166:Immunosuppressive Agents; D007555:Isoxazoles; D000068338:Everolimus; D000077339:Leflunomide
keywords: BK nephropathy; Everolimus; Leflunomide; polyomavirus