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 = 5), cyclosporine (CyA) nephrotoxicity (n = 4) or biopsy-proven CAN (n = 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±0.6mg/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 -5±21%/6 months postconversion to LEF (p=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 = NS. Conversion to LEF reversed progression of chronic renal allograft dysfunction with minimal toxicity.
- Chronic allograft nephropathy
ASJC Scopus subject areas
- Immunology and Allergy
- Pharmacology (medical)