본문 바로가기
KERD
논문KCI 등재

Safety and immunologic benefits of conversion to sirolimus in kidney transplant recipients with long-term exposure to calcineurin inhibitors

1

조회

0

다운로드

0

인용

0

참고문헌

키워드

주제분류내과학

초록

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.

참고문헌 (21)

  1. Li C, "The pathogenesis and treatment of chronic allograft nephropathy", Nat Rev Nephrol, 5, pp.513~519 (2009)
  2. Kasiske BL, "Cancer after kidney transplantation in the United States", Am J Transplant, 4, pp.905~913 (2004)
  3. Vincenti F, "Results of an international, randomized trial comparing glucose metabolism disorders and outcome with cyclosporine versus tacrolimus", Am J Transplant, 7, pp.1506~1514 (2007)
  4. Stallone G, "Sirolimus for Kaposi’s sarcoma in renal-transplant recipients", N Engl J Med, 352, pp.1317~1323 (2005)
  5. Saemann MD, "The multifunctional role of mTOR in innate immunity: implications for transplant immunity", Am J Transplant, 9, pp.2655~2661 (2009)
  6. Zhao T, "Comparison of regulatory T cells and FoxP3-positive T-cell subsets in the peripheral blood of renal transplant recipients with sirolimus versus cyclosporine: a preliminary study", Transplant Proc, 45, pp.148~152 (2013)
  7. Stallone G, "Rapamycin for treatment of chronic allograft nephropathy in renal transplant patients", J Am Soc Nephrol, 16, pp.3755~3762 (2005)
  8. Schena FP, "Conversion from calcineurin inhibitors to sirolimus maintenance therapy in renal allograft recipients: 24-month efficacy and safety results from the CONVERT trial", Transplantation, 87, pp.233~242 (2009)
  9. Weir MR, "Mycophenolate mofetil-based immunosuppression with sirolimus in renal transplantation: a randomized, controlled Spare-the-Nephron trial", Kidney Int, 79, pp.897~907 (2011)
  10. Guba M, "Early conversion to a sirolimus-based, calcineurin-inhibitor-free immunosuppression in the SMART trial: observational results at 24 and 36months after transplantation", Transpl Int, 25, pp.416~423 (2012)
  11. Soleimani AR, "Comparison of cyclosporine and sirolimus effects on serum creatinine level over five years after kidney transplantation", Transplant Proc, 45, pp.1644~1647 (2013)
  12. Diekmann F, "Conversion from calcineurin inhibitors to sirolimus in chronic allograft nephropathy:benefits and risks", Nephrol Dial Transplant, 21, pp.562~568 (2006)
  13. Alvarez-Lara MA, "The imbalance in the ratio of Th1 and Th2 helper lymphocytes in uraemia is mediated by an increased apoptosis of Th1subset", Nephrol Dial Transplant, 19, pp.3084~3090 (2004)
  14. Lebranchu Y, "Efficacy on renal function of early conversion from cyclosporine to sirolimus 3 months after renal transplantation: concept study", Am J Transplant, 9, pp.1115~1123 (2009)
  15. Guba M, "Renal function, efficacy, and safety of sirolimus and mycophenolate mofetil after short-term calcineurin inhibitor-based quadruple therapy in de novo renal transplant patients: one-year analysis of a randomized multicenter trial", Transplantation, 90, pp.175~183 (2010)
  16. Li Y, "CNI induced Th17", Treg imbalance and susceptibility to renal dysfunction in renal transplantation, 2011, pp.11, 2033~2038
  17. Chung BH, "Dysregulation of Th17 cells during the early post-transplant period in patients under calcineurin inhibitor based immunosuppression", PLoS One, 7, pp.e42011~ (2012)
  18. Kim KW, "The effect of mammalian target of rapamycin inhibition on T helper type 17 and regulatory T cell differentiation in vitro and in vivo in kidney transplant recipients", Immunology, 144, pp.68~78 (2015)
  19. Yap M, "Expansion of highly differentiated cytotoxic terminally differentiated effector memory CD8+ T cells in a subset of clinically stable kid-ney transplant recipients: a potential marker for late graft dysfunction", J Am Soc Nephrol, 25, pp.1856~1868 (2014)
  20. Pallet N, "Adverse events associated with mTOR inhibitors", Expert Opin Drug Saf, 12, pp.177~186 (2013)
  21. Chuang P, "Clobetasol ameliorates aphthous ulceration in renal transplant patients on sirolimus", Am J Transplant, 7, pp.714~717 (2007)

관련 논문AI추천

실제 임상현장에서의 간이식 환자 대상 Everolimus와 저용량 Tacrolimus 병용요법의 유효성 및 안전성 평가김보람, 이은숙, 이주연, 장서윤, 전수정, 조재영, 최경숙, 한호성, Eunkyung Euni Lee한국임상약학회 · 한국임상약학회지2021 · 제31권 제1호Bisphosphonates as a Tacrolimus-Sparing Strategy in Kidney Transplantation: Insights from a Retrospective Analysis고희병, 김범석, 김형우, 김효정, 남정모, 송승환, 양재석, 이예지, 정찬영, 최훈영, 허가영, 허규하, 홍남기연세대학교의과대학 · Yonsei Medical Journal2026 · 제67권 제1호1일 2회 투여하는 Tacrolimus에서 1일 1회 투여하는 서방형 Tacrolimus로 전환 시 대응 용량비의 적절성 평가권은영, 김혜영, 박소연, 오미란, 윤정이, 이성민, 황보신이한국병원약사회 · 병원약사회지2020 · 제37권 제1호폐 이식 후 신부전 발생 환자에서 유지 면역억제제로서 basiliximab의 사용 평가금민정, 김재송, 서예진, 손은선, 유윤미, 이경아한국임상약학회 · 한국임상약학회지2020 · 제30권 제3호Usefulness of valacyclovir prophylaxis for cytomegalovirus infection after anti-thymocyte globulin as rejection therapy고은정, 양철우, 유지현, 정병하대한내과학회 · The Korean Journal of Internal Medicine2019 · 제34권 제2호Review of two immunosuppressants: tacrolimus and cyclosporineHoon Myoung, HyunJong Lee, Soung Min Kim대한구강악안면외과학회 · 대한구강악안면외과학회지2023 · 제49권 제6호

이 간행물의 다른 논문 (26건)