Leflunomide Therapy for Polyomavirus-Induced Allograft Nephropathy: Efficient BK Virus Elimination Without Increased Risk of Rejection

• Published in: Transplantation proceedings Vol. 41; no. 6; pp. 2533 - 2538
• Main Authors: Teschner, S, Gerke, P, Geyer, M, Wilpert, J, Krumme, B, Benzing, T, Walz, G
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Amsterdam Elsevier Inc 01.07.2009; Elsevier
• Subjects: Antiviral Agents - therapeutic use; Biological and medical sciences; Biopsy; BK Virus - drug effects; Dose-Response Relationship, Drug; Drug Monitoring - methods; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Graft Rejection - epidemiology; Humans; Immunosuppressive Agents - therapeutic use; Infectious diseases; Isoxazoles - blood; Isoxazoles - therapeutic use; Kidney Transplantation - adverse effects; Kidney Transplantation - pathology; Medical sciences; Mycophenolic Acid - analogs & derivatives; Mycophenolic Acid - therapeutic use; Polyomavirus Infections - prevention & control; Risk Factors; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Tissue, organ and graft immunology; Viral diseases; Viral Load; Prostaglandin-endoperoxide synthase; Graft(material); Isoxazole derivatives; Homograft; Risk; Transplantation; Papovaviridae; Leflunomide; Surgery; Graft; Antirheumatic agent; Kidney disease; Opportunistic infection; Urinary system disease; Enzyme; Elimination; Polyomavirus; Enzyme inhibitor; BK virus; Infection; Virus; Non steroidal antiinflammatory agent; Medicine; Rejection; Nephropathy; Treatment; Viral disease; Risk factor; Oxidoreductases; Immunosuppressive agent
• ISSN: 0041-1345; 1873-2623
• 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.