Leflunomide (LEF) is a synthetic isoxazole derivative with anti-inflammatory and antiviral properties, which has been reported to prevent acute rejection and delay progression of chronic allograft nephropathy (CAN) in animal models. We performed a pilot, crossover trial in 22 renal transplant recipients who were converted from azathioprine (AZA) or mycophenolate mofetil (MMF) to LEF in an effort to slow progression of renal dysfunction [deteriorating renal function (n Ω 5), cyclosporine (CyA) nephrotoxicity (n Ω 4) or biopsy-proven CAN (n Ω 13)]. Baseline maintenance immunosuppression consisted of CyA, AZA or MMF and prednisone. Six-month postconversion patient and graft survival was 100% and 91%, respectively. Mean serum creatinine 6 months preconversion was 2.2 ∫ 0.6 mg/dL, at initiation was 3.0 ∫ 1.1 mg/dL, and 6 months postconversion was 2.8 ∫ 1.3 mg/dL. The rate of change in serum creatinine was 35 ∫ 39%/6 months preconversion and ª5 ∫ 21%/6 months postconversion to LEF (p Ω 0.003). Two patients discontinued LEF for diarrhea and myalgia. No readmissions, increase in liver function tests, infections or acute rejection episodes occurred. Mean CyA levels did not change, 146 ∫ 72 ng/ mL pre-LEF vs. 132 ∫ 51 ng/mL post-LEF, p Ω NS. Conversion to LEF reversed progression of chronic renal allograft dysfunction with minimal toxicity.
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