Abstract
Polyomavirus-associated nephropathy (PVAN) remains a relevant complication following kidney transplantation with allograft loss rates of up to 50%. Reduction in overall immunosuppression is a cornerstone of therapy, whereas no specific antiviral regimen has shown conclusive benefit to date. The present case series demonstrates the efficacy of a dual therapeutic approach with low-dose cidofovir and conversion to mTOR-based immunosuppression in PVAN. Patients with biopsy-proven PVAN having received low-dose cidofovir (0.25mg/kg) according to the Tübingen Cidofovir Protocol and been converted to mTOR-based immunosuppression were analyzed retrospectively. Twenty-three patients with a median follow-up of 2.24 [IQR 1.55-5.01] years were included in the analysis. Median time to PVAN diagnosis was 268 [IQR 153-869] days after transplantation. Polyomavirus clearance from plasma was achieved in 78% of patients after a median of 118 [IQR 76-293] days. Of the 23 patients, nine patients (39%) lost their allograft function during follow-up, but only three of these (13%) due to PVAN. Fourteen patients (61%) stabilized or improved allograft function. The cidofovir protocol allowed for specific antiviral therapy without adverse nephrotoxicity, even in patients with low allograft function. Low-dose cidofovir and conversion to mTOR-based immunosuppression allow for effective virus clearance and preservation of allograft function in a high proportion of patients with PVAN and progressive allograft dysfunction and may prolong allograft survival in these patients.
Highlights
With the introduction of potent immunosuppressive regimens, polyomavirus-associated nephropathy (PVAN) has emerged as a relevant infectious complication, affecting 1-10% of the kidney transplant recipients [1,2]
Background: Polyomavirus-associated nephropathy (PVAN) remains a relevant complication following kidney transplantation with allograft loss rates of up to 50%
We present data from our kidney transplant center focusing on probability and time course of BK-virus clearance as well as allograft function in kidney transplant recipients with biopsy proven PVAN, treated with a novel dual therapeutic approach consisting of low-dose cidofovir together with conversion to mTOR-based immunosuppression
Summary
With the introduction of potent immunosuppressive regimens, polyomavirus-associated nephropathy (PVAN) has emerged as a relevant infectious complication, affecting 1-10% of the kidney transplant recipients [1,2]. A number of studies have shown benefits of an mTOR-inhibitor based immunosuppression regarding the risk of BK-viremia compared to the standard of care tacrolimus-based regimen [12,13], limited data exist on effectiveness of this strategy in case of a biopsy proven polyomavirus-nephropathy. The rationale for this treatment approach relies on the interaction of BK-virus replication with components of the mTOR pathway as well as data showing an increased differentiation of virus-specific CD8+-memory T-cells [14,15,16] following mTOR-inhibition. Conclusions: Low-dose cidofovir and conversion to mTOR-based immunosuppression allow for effective virus clearance and preservation of allograft function in a high proportion of patients with PVAN and progressive allograft dysfunction and may prolong allograft survival in these patients
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