BK Nephropathy in Kidney Transplant Recipients Treated with a Calcineurin Inhibitor-Free Immunosuppression Regimen

Department of Surgery, University of California-San Francisco, San Francisco, California, USA.
American Journal of Transplantation (Impact Factor: 5.68). 01/2005; 4(12):2132-4. DOI: 10.1046/j.1600-6143.2004.00600.x
Source: PubMed


Recently, polyomavirus-associated nephropathy (PVAN) has been reported more frequently and is emerging as an important cause of renal allograft dysfunction and graft loss. Susceptibility appears to be related to the type and intensity of pharmacologic immunosuppression but some reports have suggested a link among the development of PVAN, the treatment of rejection or maintenance with a tacrolimus-based immunosuppressive regimen. We report three cases of PVAN in patients who never received immunosuppression with calcineurin inhibitors (CNIs). Two patients received induction immunosuppression consisting of an IL-2 receptor antagonist while 1 received thymoglobulin. These 3 patients were maintained on prednisone, sirolimus and mycophenolate mofetil (MMF) and none was treated for rejection. All three patients presented with an elevated serum creatinine and demonstrated polyomavirus infection on biopsy and by blood PCR. These cases demonstrate that, unlike reports linking tacrolimus and PVAN, polyomavirus infection may develop in patients maintained on CNI-free immunosuppressive regimens and have not had episodes of rejection.

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Available from: Stuart M Flechner, Nov 10, 2014
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    • "A randomized, single-center trial comparing CsA vs tacrolimus used BKN as a primary end point; but because no cases of BKN occurred before the last study visit in either trial, the risk associated with choice of CNI could not be assessed [9]. However, because the presence of BK viruria and/or viremia shows a close association with BKN and subsequent graft loss [36] [37], the relationship between CNIs and urine or plasma positivity is also important. In the prospective DIRECT study [38] [39] [40], in which de novo kidney transplant recipients were randomized to CsA or tacrolimus, both with MPA and corticosteroids, BK viremia was a predefined secondary end point. "
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    ABSTRACT: The increasing incidence of BK-associated nephropathy following kidney transplantation has prompted an examination of strategies for risk reduction and management through immunosuppression manipulation. Evidence from retrospective and prospective studies suggests that BK viruria and viremia, and the need for BK virus treatment, are higher with tacrolimus than cyclosporine. Combined therapy with tacrolimus and mycophenolic acid may be associated with a particularly higher risk of BK infection, but data are conflicting as to whether mycophenolic acid per se is an independent risk factor. The incidence of BK-related events may be reduced in patients receiving mTOR inhibitors (everolimus or sirolimus) with cyclosporine vs a calcineurin inhibitor with mycophenolic acid. De novo immunosuppression regimens that avoid rabbit antithymocyte globulin and tacrolimus, particularly tacrolimus with mycophenolic acid, may be advantageous, whereas low-exposure cyclosporine with an mTOR inhibitor appears a favorable option. Routine screening for BK infection during the first 2 years posttransplant is recommended to allow preemptive modification of the immunosuppressive regimen. In patients at high risk of BK virus infection, appropriate de novo immunosuppression or very early conversion to an mTOR inhibitor to facilitate reduction or discontinuation of calcineurin inhibitors or antimetabolites should be considered. Extensive further research into optimal avoidance, screening, and treatment strategies is required.
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    ABSTRACT: With the introduction of more potent immunosuppressive agents, rejection has decreased in simultaneous pancreas/kidney transplant (SPK) recipients. However, as a consequence, opportunistic infections have increased. The purpose of this report is to outline the course of SPK patients who developed polyomavirus-associated nephropathy (PVAN). A retrospective review of 146 consecutive SPK recipients from January 1, 1996 to December 31, 2002 was performed. Immunosuppression, rejection and development of PVAN were reviewed. Nine patients were identified. All received induction with either OKT3 or thymoglobulin. Immunosuppression included tacrolimus/cyclosporine, MMF/azathioprine and sirolimus/prednisone. Two patients were treated for kidney rejection prior to the diagnosis of PVAN. Time to diagnosis was an average of 359.3 days post-transplantation. Immunosuppression was decreased but five ultimately lost function. However, none developed pancreatic abnormalities as demonstrated by normal glucose and amylase. Two underwent renal retransplantation after PVAN diagnosis and both have normal kidney function. PVAN was the leading cause of renal loss in SPK patients in the first 2 years after transplantation and is a serious concern for SPK recipients. The pancreas, however, is spared from evidence of infection, and no pancreatic rejection occurred when immunosuppression was decreased.
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