Higher levels of leflunomide are associated with hemolysis and are not superior to lower levels for BK virus clearance in renal transplant patients

Clin J Am Soc Nephrol. 2008 May;3(3):829-35. doi: 10.2215/CJN.03930907. Epub 2008 Mar 27.

Abstract

Background and objectives: Leflunomide use in renal transplantation has been increasing. Outcome correlation and safety data are still to be refined. The goals of this study were to report one center's experience with leflunomide, specifically the correlation of leflunomide levels with the outcomes of BK nephropathy and the observed toxic effects during the treatment with leflunomide.

Design, setting, participants, & measurements: Leflunomide was used in 21 patients with BK nephropathy. These patients were divided into two groups on the basis of the leflunomide levels achieved: Low-level group (<40 microg/ml) and high-level group (>40 microg/ml).

Results: During 13 mo of follow-up, there was no difference in the rate of serum BK viral clearance between the groups. There were three graft losses in the low-level group and one in the high-level group; however, creatinine levels were higher at the time of starting leflunomide in the low-level group. Leflunomide was also used in six patients with chronic allograft injury. No graft loss was observed during the follow-up period of 16 mo. Treatment with leflunomide seemed to be associated with a new toxicity, hemolysis, seen in four of the 27 patients so treated. Patients with hemolysis had high leflunomide levels (81.4 +/- 14 microg/ml) and worsening allograft function. Two patients had histologic evidence of thrombotic microangiopathy, which led to graft loss in one patient.

Conclusions: The clinical correlation between leflunomide levels and outcomes needs to be further refined. This study described a possible association of leflunomide with thrombotic microangiopathy, especially at higher levels.

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / adverse effects*
  • BK Virus / drug effects*
  • Dose-Response Relationship, Drug
  • Female
  • Graft Rejection / prevention & control*
  • Graft Rejection / virology
  • Hemolysis / drug effects*
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Isoxazoles / adverse effects*
  • Kidney / drug effects*
  • Kidney / pathology
  • Kidney / surgery
  • Kidney / virology
  • Kidney Transplantation*
  • Leflunomide
  • Male
  • Middle Aged
  • Polyomavirus Infections / drug therapy*
  • Polyomavirus Infections / pathology
  • Polyomavirus Infections / virology
  • Retrospective Studies
  • Thrombosis / chemically induced
  • Time Factors
  • Viral Load

Substances

  • Antiviral Agents
  • Immunosuppressive Agents
  • Isoxazoles
  • Leflunomide