Prospective, pilot, open-label, short-term study of conversion to leflunomide reverses chronic renal allograft dysfunction

Karen L. Hardinger, Candace D. Wang, Mark A. Schnitzler, Brent W. Miller, Martin D. Jendrisak, Surendra Shenoy, Jeffery A. Lowell, Daniel C. Brennan

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)867-871
Number of pages5
JournalAmerican Journal of Transplantation
Volume2
Issue number9
DOIs
StatePublished - Oct 1 2002
Externally publishedYes

Keywords

  • Chronic allograft nephropathy
  • Conversion
  • Leflunomide

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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