Treatment and Management
Management of PVAN is directed at eliminating the virus, avoiding acute rejection, and preserving renal function. Interventions include the reduction of immunosuppression, with or without provision of antiviral therapy. Methods for reducing immunosuppression vary greatly, but can be generally categorized as follows: reduction in the dose of two agents; discontinuation of one agent; or transition from one agent to another. No randomized trial has compared reduction strategies, although in a retrospective, nonrandomized trial, Wadei et al. found no difference in graft outcomes when patients who were switched from a tacrolimus-based regimen to a low-dose ciclosporin-based regimen were compared to those who underwent tacrolimus dose reduction. Various case series have suggested additional interventions to be of benefit in PVAN. Leflunomide, an immunosuppressive agent commonly used in rheumatoid arthritis, has antiviral activity against polyomavirus in vitro and in animals. One case series reported a marked reduction in viremia and viruria with stabilization of renal function in patients who tolerated leflunomide (dosed to a target trough level of 50–100 µg/ml), but these outcomes have not been universally noted. Cidofovir, an antiviral agent approved for the treatment of cytomegalovirus, has been reported to be of benefit in selected patients who did not respond to a reduction in immunosuppression alone, but it has modest mechanistic effect against BK virus in vitro, and its clinical utility is uncertain because of its potential to cause nephrotoxic effects. In the setting of PVAN, the dose of cidofovir is 10–20% of that used for the treatment of cytomegalovirus. Similar to cidofovir, fluoroquinolones such as ciprofloxacin have a modest in vitro anti-BK-virus effect and may have a role in polyomavirus suppression. Finally, intravenous immunoglobulin has been proposed to be both a treatment for PVAN and a preventative strategy to avoid acute rejection during immunosuppression reduction in renal transplant recipients. In the patient presented here, aggressive immunosuppression reduction was combined with the addition of leflunomide, and plasma viral load was monitored to document clearance of viremia. At 7 months, BK viremia was undetectable and the patient had stable renal function. An improved outcome, with renal function recovery to a greater extent than was achieved in this case, might have been achieved if polyomavirus screening had been performed in the months before biopsy, and if viremia could have been cleared more rapidly, potentially via loading doses of leflunomide, addition of cidofovir, or further reduction in ciclosporin dose. Following the initial management of PVAN, it is imperative that a patient's glomerular filtration rate and BK viremia are monitored serially, and that a repeat biopsy is performed in the event of deterioration of either parameter. Retransplantation remains an option in cases of graft loss.
Nat Clin Pract Nephrol. 2008;4(5):283-287. © 2008
Nature Publishing Group
Cite this: A Case of Polyomavirus-associated Nephropathy Presenting Late After Transplantation - Medscape - May 01, 2008.