Prospective, pilot, open-label, short-term study of conversion to leflunomide reverses chronic renal allograft dysfunction.
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 6months 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.
Hardinger
Karen L
KL
Department of Pharmacy, Barnes-Jewish Hospital, Washington University, St Louis, MO, USA. klh2562@bjc.org
Wang
Candace D
CD
Schnitzler
Mark A
MA
Miller
Brent W
BW
Jendrisak
Martin D
MD
Shenoy
Surendra
S
Lowell
Jeffery A
JA
Brennan
Daniel C
DC
D000328:Adult; D001379:Azathioprine / Q000494:pharmacology; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007555:Isoxazoles / Q000008:administration & dosage / Q000494:pharmacology*; D016030:Kidney Transplantation / Q000276:immunology*; D000077339:Leflunomide; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000494:pharmacology
D007166:Immunosuppressive Agents; D007555:Isoxazoles; D000077339:Leflunomide; D009173:Mycophenolic Acid; D001379:Azathioprine