Safety and immunologic benefits of conversion to sirolimus in kidney transplant recipients with long-term exposure to calcineurin inhibitors
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Background/Aims: Sirolimus (SRL) is a promising immunosuppressant replacing calcineurin inhibitors (CNIs). This study was performed to evaluate the safety and immunologic benefits of conversion to SRL in stable kidney transplant (KT) recipients exposed to CNIs for long periods. Methods: Fourteen CNI-treated KT recipients with stable renal function for more than 10 years were included. Either 2 or 3 mg per day of SRL was administered while CNIs were reduced by half starting on day 1, and then stopped 2 weeks after SRL introduction. The safety of SRL conversion was assessed considering the graft function, acute rejection, and graft loss. Immunologic alterations were measured via serial changes of T cell and B cell subsets after SRL conversion. Adverse effects of SRL conversion were also evaluated. Results: Conversion to SRL was successful in nine patients (64.2%). Conversion to SRL preserved graft function as compared to the baseline value (p = 0.115). No acute rejection or allograft loss was observed during the follow-up period. Immune monitoring of T and B cells revealed a regulatory T cells increase after SRL conversion (p = 0.028). Most adverse events developed within 6 weeks after SRL conversion, and oral mucositis was the main cause of SRL withdrawal. Conclusions: Conversion to SRL can be safe and has immunologic benefits in KT recipients with long-term CNI exposure. Close monitoring of mucocutaneous adverse events is, however, required in the early period after SRL conversion.
Abstract
Background/Aims: Sirolimus (SRL) is a promising immunosuppressant replacing calcineurin inhibitors (CNIs). This study was performed to evaluate the safety and immunologic benefits of conversion to SRL in stable kidney transplant (KT) recipients exposed to CNIs for long periods. Methods: Fourteen CNI-treated KT recipients with stable renal function for more than 10 years were included. Either 2 or 3 mg per day of SRL was administered while CNIs were reduced by half starting on day 1, and then stopped 2 weeks after SRL introduction. The safety of SRL conversion was assessed considering the graft function, acute rejection, and graft loss. Immunologic alterations were measured via serial changes of T cell and B cell subsets after SRL conversion. Adverse effects of SRL conversion were also evaluated. Results: Conversion to SRL was successful in nine patients (64.2%). Conversion to SRL preserved graft function as compared to the baseline value (p = 0.115). No acute rejection or allograft loss was observed during the follow-up period. Immune monitoring of T and B cells revealed a regulatory T cells increase after SRL conversion (p = 0.028). Most adverse events developed within 6 weeks after SRL conversion, and oral mucositis was the main cause of SRL withdrawal. Conclusions: Conversion to SRL can be safe and has immunologic benefits in KT recipients with long-term CNI exposure. Close monitoring of mucocutaneous adverse events is, however, required in the early period after SRL conversion.
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