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: 6.19). 01/2005; 4(12):2132-4. DOI: 10.1046/j.1600-6143.2004.00600.x
Source: PubMed

ABSTRACT 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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    ABSTRACT: Overimmunosuppression is a widely recognized risk factor for BK virus (BKV) infection, particularly with the combination of tacrolimus, mycophenolate mofetil (MMF), and steroids. Nevertheless, the exact impact of exposure to tacrolimus and MMF is not well understood. We examined 240 kidney recipients between 2006 and 2008. BKV was monitored every 2 months in the urine or blood. A kidney biopsy was performed when viremia exceeded 10 copies/mL. Ninety-five (40%) patients had sustained viruria, 48 (20%) sustained viremia, and 17 (7%) biopsy-proven polyomavirus-associated nephropathy. The mean time-to-occurrence was 7.6, 7.9, and 9.7 months for viruria, viremia, and polyomavirus-associated nephropathy. Risk factors associated with BKV infection in univariate analyses were retransplantation, panel-reactive antibody more than 0%, cytomegalovirus D+/R-, cold ischemia time, delayed graft function, induction with antithymocyte globulins, acute rejection before month 3 (M3), tacrolimus trough levels more than 10 ng/mL, and M3 AUC0-12 hr more than 50 hr mg/L. Multivariate analyses showed that cytomegalovirus D+/R- (adjusted hazard ratio [AHR], 2.03; P=0.05), acute rejection (AHR, 5.4; P<0.001), and mycophenolic acid AUC0-12 hr more than 50 hr mg/L (AHR, 3.6; P=0.001) were risk factors for BKV. This study identified a link between a state of increased immunosuppression and BKV infection, especially in patients with higher MMF exposure and elevated tacrolimus trough levels at M3.
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