Nicolae Leca1. 1. Department of Medicine, Division of Nephrology, University of Washington, Seattle, WA 98195, USA. nleca@u.washington.edu
Abstract
PURPOSE OF REVIEW: Leflunomide has been used off-label in renal transplantation because of the attractive combination of antiviral and immunosuppressive effects. This study intends to review the clinical applications of leflunomide with interest to transplantation. RECENT FINDINGS: In renal transplantation, particularly in BK nephropathy, the use of leflunomide has attempted to model the in-vitro antiviral experimental data, leading to the use of higher dosages than those studied in the approved use in rheumatoid arthritis. Concerns of toxicity with this approach have been raised, and a newer association with hemolysis and thrombotic microangiopathy has been reported. By attempting to target levels, the use of leflunomide in transplantation has been difficult because of the long half-life of the drug and the high interpatient variability. Higher leflunomide levels may lead to disproportionate immunosuppressive effects and decrease the antiviral properties. Newer data suggest that the correlation between leflunomide levels and BK nephropathy outcome is unclear. SUMMARY: The available clinical data with leflunomide in renal transplantation are limited; however, it suggests positive outcomes and shows that the correlation between the drug exposure and its effects has not been well delineated. Further research is needed to refine the safety and efficacy of leflunomide in relation to its potential effects in a multitude of pathological entities in renal transplantation.
PURPOSE OF REVIEW: Leflunomide has been used off-label in renal transplantation because of the attractive combination of antiviral and immunosuppressive effects. This study intends to review the clinical applications of leflunomide with interest to transplantation. RECENT FINDINGS: In renal transplantation, particularly in BK nephropathy, the use of leflunomide has attempted to model the in-vitro antiviral experimental data, leading to the use of higher dosages than those studied in the approved use in rheumatoid arthritis. Concerns of toxicity with this approach have been raised, and a newer association with hemolysis and thrombotic microangiopathy has been reported. By attempting to target levels, the use of leflunomide in transplantation has been difficult because of the long half-life of the drug and the high interpatient variability. Higher leflunomide levels may lead to disproportionate immunosuppressive effects and decrease the antiviral properties. Newer data suggest that the correlation between leflunomide levels and BK nephropathy outcome is unclear. SUMMARY: The available clinical data with leflunomide in renal transplantation are limited; however, it suggests positive outcomes and shows that the correlation between the drug exposure and its effects has not been well delineated. Further research is needed to refine the safety and efficacy of leflunomide in relation to its potential effects in a multitude of pathological entities in renal transplantation.