Use of Leflunomide in the Treatment of Polyomavirus BK-Associated Nephropathy

Abstract

To review the available literature describing the use of leflunomide for the treatment of polyomavirus BK-associated nephropathy (BKVAN) in renal transplant recipients. Relevant literature was obtained through MEDLINE (1950-May 2008) and Science Citation Index Expanded (1900-May 2008) by using search terms leflunomide, Arava, polyomavirus, polyoma, BK virus, and transplant. Additional articles were identified through a manual search of the reference lists of the articles obtained. All articles that were written in English and discussed leflunomide use for BKVAN in renal transplant recipients were evaluated. Case reports and in vitro studies were included in this review. BKVAN has emerged as a problematic infectious complication with limited treatment options in renal transplant recipients. Leflunomide, used off-label for refractory BKVAN, is postulated to possess both antiviral and immunosuppressive properties. Two in vitro culture studies, 5 case reports/series, 2 retrospective cohort studies, and 3 prospective observational trials that described leflunomide use in BKVAN were identified. Available literature suggests that leflunomide at target blood concentrations of around 40 mg/L, in addition to immunosuppressive reduction, reduces BK viremia/viruria and graft failure, with few dose-limiting adverse events. It is highly recommended that routine complete blood cell counts, hepatic function panels, and drug concentrations be monitored to detect toxicity. Leflunomide appears to be promising as adjunctive treatment of BKVAN in renal transplant patients. Due to the lack of controlled randomized trials, however, use of leflunomide as first-line treatment cannot be routinely recommended.