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http://dx.doi.org/10.3904/kjim.2014.366

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

Yu, Ji Hyun (Division of Nephrology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea)
Kim, Kyoung Woon (Convergent Research Consortium for Immunologic Disease, Seoul St. Mary's Hospital, The Catholic University of Korea)
Kim, Bo-Mi (Convergent Research Consortium for Immunologic Disease, Seoul St. Mary's Hospital, The Catholic University of Korea)
Chung, Byung Ha (Division of Nephrology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea)
Cho, Mi-La (Convergent Research Consortium for Immunologic Disease, Seoul St. Mary's Hospital, The Catholic University of Korea)
Choi, Bum Soon (Division of Nephrology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea)
Park, Cheol Whee (Division of Nephrology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea)
Kim, Yong-Soo (Division of Nephrology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea)
Yang, Chul Woo (Division of Nephrology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea)
Publication Information
The Korean journal of internal medicine / v.31, no.3, 2016 , pp. 552-559 More about this Journal
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.
Keywords
Sirolimus; Calcineurin inhibitors; Kidney transplantation;
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1 Li C, Yang CW. The pathogenesis and treatment of chronic allograft nephropathy. Nat Rev Nephrol 2009;5:513-519.
2 Kasiske BL, Snyder JJ, Gilbertson DT, Wang C. Cancer after kidney transplantation in the United States. Am J Transplant 2004;4:905-913.   DOI
3 Vincenti F, Friman S, Scheuermann E, et al. Results of an international, randomized trial comparing glucose metabolism disorders and outcome with cyclosporine versus tacrolimus. Am J Transplant 2007;7:1506-1514.   DOI
4 Stallone G, Schena A, Infante B, et al. Sirolimus for Kaposi's sarcoma in renal-transplant recipients. N Engl J Med 2005;352:1317-1323.   DOI
5 Soleimani AR, Kamkar I, Nikoueinejad H, Moraweji AR. Comparison of cyclosporine and sirolimus effects on serum creatinine level over five years after kidney transplantation. Transplant Proc 2013;45:1644-1647.   DOI
6 Diekmann F, Campistol JM. Conversion from calcineurin inhibitors to sirolimus in chronic allograft nephropathy: benefits and risks. Nephrol Dial Transplant 2006;21:562-568.   DOI
7 Alvarez-Lara MA, Carracedo J, Ramirez R, et al. The imbalance in the ratio of Th1 and Th2 helper lymphocytes in uraemia is mediated by an increased apoptosis of Th1 subset. Nephrol Dial Transplant 2004;19:3084-3090.   DOI
8 Lebranchu Y, Thierry A, Toupance O, et al. Efficacy on renal function of early conversion from cyclosporine to sirolimus 3 months after renal transplantation: concept study. Am J Transplant 2009;9:1115-1123.   DOI
9 Guba M, Pratschke J, Hugo C, et al. 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 2010;90:175-183.
10 Li Y, Shi Y, Huang Z, et al. CNI induced Th17/Treg imbalance and susceptibility to renal dysfunction in renal transplantation. Int Immunopharmacol 2011;11:2033-2038.   DOI
11 Chung BH, Kim KW, Kim BM, et al. Dysregulation of Th17 cells during the early post-transplant period in patients under calcineurin inhibitor based immunosuppression. PLoS One 2012;7:e42011.   DOI
12 Schena FP, Pascoe MD, Alberu J, et al. Conversion from calcineurin inhibitors to sirolimus maintenance therapy in renal allograft recipients: 24-month efficacy and safety results from the CONVERT trial. Transplantation 2009;87:233-242.   DOI
13 Saemann MD, Haidinger M, Hecking M, Horl WH, Weichhart T. The multifunctional role of mTOR in innate immunity: implications for transplant immunity. Am J Transplant 2009;9:2655-2661.   DOI
14 Zhao T, Yang C, Qiu Y, et al. 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 2013;45:148-152.   DOI
15 Stallone G, Infante B, Schena A, et al. Rapamycin for treatment of chronic allograft nephropathy in renal transplant patients. J Am Soc Nephrol 2005;16:3755-3762.   DOI
16 Weir MR, Mulgaonkar S, Chan L, et al. Mycophenolate mofetil-based immunosuppression with sirolimus in renal transplantation: a randomized, controlled Spare-the-Nephron trial. Kidney Int 2011;79:897-907.   DOI
17 Pallet N, Legendre C. Adverse events associated with mTOR inhibitors. Expert Opin Drug Saf 2013;12:177-186.   DOI
18 Guba M, Pratschke J, Hugo C, et al. Early conversion to a sirolimus-based, calcineurin-inhibitor-free immunosuppression in the SMART trial: observational results at 24 and 36months after transplantation. Transpl Int 2012;25:416-423.   DOI
19 Kim KW, Chung BH, Kim BM, Cho ML, Yang CW. 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 2015;144:68-78.   DOI
20 Yap M, Boeffard F, Clave E, et al. 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 2014;25:1856-1868.   DOI
21 Chuang P, Langone AJ. Clobetasol ameliorates aphthous ulceration in renal transplant patients on sirolimus. Am J Transplant 2007;7:714-717.   DOI