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Prospective, Pilot, Open‐Label, Short‐Term Study of Conversion to Leflunomide Reverses Chronic Renal Allograft Dysfunction
Author(s) -
Hardinger Karen L.,
Wang Candace D.,
Schnitzler Mark A.,
Miller Brent W.,
Jendrisak Martin D.,
Shenoy Surendra,
Lowell Jeffery A.,
Brennan Daniel C.
Publication year - 2002
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1034/j.1600-6143.2002.20909.x
Subject(s) - medicine , leflunomide , azathioprine , gastroenterology , urology , creatinine , immunosuppression , renal function , nephrotoxicity , nephropathy , prednisone , mycophenolic acid , chronic allograft nephropathy , toxicity , transplantation , kidney transplantation , rheumatoid arthritis , endocrinology , diabetes mellitus , disease
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 ± 0.6 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 − 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.