Leflunomide Efficacy and Pharmacodynamics for the Treatment of BK Viral Infection

作者:Krisl Jill C*; Taber David J; Pilch Nicole; Chavin Kenneth; Bratton Charles; Thomas Beje; McGillicuddy John; Baliga Prabhakar
来源:Clinical Journal of the American Society of Nephrology, 2012, 7(6): 1003-1009.
DOI:10.2215/CJN.12531211

摘要

Background and objectives BK virus is an infection in kidney transplantation patients jeopardizing graft survival. Unfortunately, there is no consensus on treatment of BK viremia and nephropathy. Leflunomide has been studied for the treatment of BK viremia and nephropathy, but there are limited data on the utility of leflunomide therapeutic drug monitoring. This study aimed to determine if a pharmacodynamic relationship exists between BK viral load reduction and leflunomide metabolite, A77 1726, serum concentrations. %26lt;br%26gt;Design, setting, participants, %26 measurements This study was a retrospective, single-center, longitudinal analysis of patients identified with BK viremia with or without nephropathy. Patients were grouped according to whether they received leflunomide. All BK viral PCR and A77 1726 concentrations were analyzed to determine pharmacodynamics, and were correlated with clinical outcomes. %26lt;br%26gt;Results Of 76 patients identified, 52 received leflunomide therapy and 24 did not. Patients who received leflunomide were further analyzed according to A77 1726 concentrations and BK clearance; there was no difference in BK clearance. There was a lack of correlation between A77 1726 concentrations and log change in BK viral PCR concentration. Multivariate analysis demonstrated that mycophenolate mofetil discontinuation, BK viremia without nephropathy, and mean BK viral load were significantly associated with BK viral clearance; leflunomide use lacked this association. %26lt;br%26gt;Conclusions Pharmacodynamic analysis revealed no association between A77 1726 concentrations and BK viral PCR reductions. Multivariate analysis demonstrated that leflunomide therapy was not associated with BK viral clearance. Randomized studies are needed to determine the utility of leflunomide for BK viremia and nephropathy. Clin J Am Soc Nephrol 7: 1003-1009, 2012. doi: 10.2215/CJN.12531211

  • 出版日期2012-6