Leflunomide therapy for polyomavirus-induced allograft nephropathy: efficient BK virus elimination without increased risk of rejection

Transplant Proc. Jul-Aug 2009;41(6):2533-8. doi: 10.1016/j.transproceed.2009.06.099.

Abstract

Background: Optimal treatment of polyomavirus-induced allograft nephropathy (PVAN) with immunosuppressive and antiviral therapy is uncertain at present. Reduced immunosuppression is accompanied by increased risk of rejection, and antiviral agents are nephrotoxic. Leflunomide has immunosuppressive and antiviral properties and may be an alternative treatment agent. We report a two-center experience with use of leflunomide for treatment of PVAN.

Patients and methods: Thirteen renal allograft recipients were diagnosed with biopsy-proven PVAN. Treatment consisted of lowering the calcineurin-inhibitor trough level, discontinuing mycophenolate mofetil therapy, and initiating leflunomide therapy. In 8 of the 13 patients, the serum concentration of the leflunomide active metabolite A771726 was monitored.

Results: Exchange of mycophenolate mofetil with leflunomide in patients with PVAN was well tolerated and safe, with no serious adverse effects or episodes of graft rejection. Mean follow-up after transplantation was 717 days, and after initiation of leflunomide therapy was 465 days. With the modified therapy, 12 patients cleared the virus at a mean of 109 days. One graft was lost due to refractory rejection accompanied by a decreasing viral load. In the other 12 patients, graft function stabilized or improved (mean [median] creatinine concentration at diagnosis, 2.39 [2.5] mg/mL, vs 2.27 [2.0] mg/dL at follow-up). Leflunomide concentration did not correlate with treatment efficiency.

Conclusions: Treatment of PVAN with leflunomide, a low-dose calcineurin inhibitor, and prednisone seems to reduce viral load and stabilize renal graft function without increasing the risk of rejection. Even low serum concentrations of leflunomide support viral elimination and prevention of graft rejection.

MeSH terms

  • Antiviral Agents / therapeutic use*
  • BK Virus / drug effects*
  • Biopsy
  • Dose-Response Relationship, Drug
  • Drug Monitoring / methods
  • Graft Rejection / epidemiology
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Isoxazoles / blood
  • Isoxazoles / therapeutic use*
  • Kidney Transplantation / adverse effects*
  • Kidney Transplantation / pathology
  • Leflunomide
  • Mycophenolic Acid / analogs & derivatives
  • Mycophenolic Acid / therapeutic use
  • Polyomavirus Infections / prevention & control*
  • Risk Factors
  • Viral Load

Substances

  • Antiviral Agents
  • Immunosuppressive Agents
  • Isoxazoles
  • Leflunomide
  • Mycophenolic Acid