Leflunomide Therapy in Kidney Transplantation

BK polyomavirus has become a scourge in kidney transplantation, mediating graft loss with progressive tubular cell death and interstitial inflammation and fibrosis (1). In the setting of immunosuppression, the virus reactivates, replicating along the tubular epithelium, spreading to other uninfected tubules, entering the tubular lumen after cell lysis, and eventually entering the bloodstream through destruction of peritubular capillaries (2). Whereas viruria is common, viremia occurs in only 13% of recipients, and nephropathy in 8% (3). Once a diagnosis is established by transplant biopsy and viral load measurements, the primary treatment strategy is immunousuppressive withdrawal (4). Disease that is more fully progressed may be unresponsive to any manipulation. Adjuvant therapies have included intravenous immune globulin, quinolones, and cidofovir, all with varying results (5). Center-specific experiences have been reported, but there are no definitive treatments.Leflunomide is an immunosuppressive agent approved for use in rheumatoid arthritis. Metabolized by the liver, the active metabolite A77 1726 blocks tyrosine kinase activity as well as pyrimidine synthesis. Leflunomide also has antiviral activity against cytomegalovirus replication in vitro and in rodent models. Although limited, initial experience in kidney transplant recipients demonstrated significant interpatient …