Comparison of 2 Immunosuppression Minimization Strategies in Kidney Transplantation: The ALLEGRO Trial.
Journal
Transplantation
ISSN: 1534-6080
Titre abrégé: Transplantation
Pays: United States
ID NLM: 0132144
Informations de publication
Date de publication:
30 Aug 2023
30 Aug 2023
Historique:
medline:
31
8
2023
pubmed:
31
8
2023
entrez:
31
8
2023
Statut:
aheadofprint
Résumé
Evidence on the optimal maintenance of immunosuppressive regimen in kidney transplantation recipients is limited. The Amsterdam, LEiden, GROningen trial is a randomized, multicenter, investigator-driven, noninferiority, open-label trial in de novo kidney transplant recipients, in which 2 immunosuppression minimization strategies were compared with standard immunosuppression with basiliximab, corticosteroids, tacrolimus, and mycophenolic acid. In the minimization groups, either steroids were withdrawn from day 3, or tacrolimus exposure was reduced from 6 mo after transplantation. The primary endpoint was kidney transplant function at 24 mo. A total of 295 participants were included in the intention-to-treat analysis. Noninferiority was shown for the primary endpoint; estimated glomerular filtration rate at 24 mo was 45.3 mL/min/1.73 m2 in the early steroid withdrawal group, 49.0 mL/min/1.73 m2 in the standard immunosuppression group, and 44.7 mL/min/1.73 m2 in the tacrolimus minimization group. Participants in the early steroid withdrawal group were significantly more often treated for rejection (P = 0.04). However, in this group, the number of participants with diabetes mellitus during follow-up and total cholesterol at 24 mo were significantly lower. Tacrolimus minimization can be considered in kidney transplant recipients who do not have an increased immunological risk. Before withdrawing steroids the risk of rejection should be weighed against the potential metabolic advantages.
Sections du résumé
BACKGROUND
BACKGROUND
Evidence on the optimal maintenance of immunosuppressive regimen in kidney transplantation recipients is limited.
METHODS
METHODS
The Amsterdam, LEiden, GROningen trial is a randomized, multicenter, investigator-driven, noninferiority, open-label trial in de novo kidney transplant recipients, in which 2 immunosuppression minimization strategies were compared with standard immunosuppression with basiliximab, corticosteroids, tacrolimus, and mycophenolic acid. In the minimization groups, either steroids were withdrawn from day 3, or tacrolimus exposure was reduced from 6 mo after transplantation. The primary endpoint was kidney transplant function at 24 mo.
RESULTS
RESULTS
A total of 295 participants were included in the intention-to-treat analysis. Noninferiority was shown for the primary endpoint; estimated glomerular filtration rate at 24 mo was 45.3 mL/min/1.73 m2 in the early steroid withdrawal group, 49.0 mL/min/1.73 m2 in the standard immunosuppression group, and 44.7 mL/min/1.73 m2 in the tacrolimus minimization group. Participants in the early steroid withdrawal group were significantly more often treated for rejection (P = 0.04). However, in this group, the number of participants with diabetes mellitus during follow-up and total cholesterol at 24 mo were significantly lower.
CONCLUSIONS
CONCLUSIONS
Tacrolimus minimization can be considered in kidney transplant recipients who do not have an increased immunological risk. Before withdrawing steroids the risk of rejection should be weighed against the potential metabolic advantages.
Identifiants
pubmed: 37650722
doi: 10.1097/TP.0000000000004776
pii: 00007890-990000000-00535
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
The authors declare no conflicts of interest.
Références
Hariharan S, Israni AK, Danovitch G. Long-term survival after kidney transplantation. N Engl J Med. 2021;385:729–743.
Gondos A, Döhler B, Brenner H, et al. Kidney graft survival in Europe and the United States: strikingly different long-term outcomes. Transplantation. 2013;95:267–274.
Coemans M, Süsal C, Döhler B, et al. Analyses of the short- and long-term graft survival after kidney transplantation in Europe between 1986 and 2015. Kidney Int. 2018;94:964–973.
Arend SM, Mallat MJ, Westendorp RJ, et al. Patient survival after renal transplantation; more than 25 years follow-up. Nephrol Dial Transplant. 1997;12:1672–1679.
Shirali AC, Bia MJ. Management of cardiovascular disease in renal transplant recipients. Clin J Am Soc Nephrol. 2008;3:491–504.
Ojo AO, Hanson JA, Wolfe RA, et al. Long-term survival in renal transplant recipients with graft function. Kidney Int. 2000;57:307–313.
Haller MC, Royuela A, Nagler EV, et al. Steroid avoidance or withdrawal for kidney transplant recipients. Cochrane Database Syst Rev. 2016;2016:CD005632.
Thomusch O, Wiesener M, Opgenoorth M, et al. Rabbit-ATG or basiliximab induction for rapid steroid withdrawal after renal transplantation (harmony): an open-label, multicentre, randomised controlled trial. Lancet. 2016;388:3006–3016.
Vincenti F, Schena FP, Paraskevas S, et al.; FREEDOM Study Group. A randomized, multicenter study of steroid avoidance, early steroid withdrawal or standard steroid therapy in kidney transplant recipients. Am J Transplant. 2008;8:307–316.
Matas AJ, Kandaswamy R, Gillingham KJ, et al. Prednisone-free maintenance immunosuppression-a 5-year experience. Am J Transplant. 2005;5:2473–2478.
Ekberg H, Tedesco-Silva H, Demirbas A, et al.; ELITE-Symphony Study. Reduced exposure to calcineurin inhibitors in renal transplantation. N Engl J Med. 2007;357:2562–2575.
Ekberg H, Bernasconi C, Tedesco-Silva H, et al. Calcineurin inhibitor minimization in the symphony study: Observational results 3 years after transplantation. Am J Transplant. 2009;9:1876–1885.
Stegall MD, Cornell LD, Park WD, et al. Renal allograft histology at 10 years after transplantation in the tacrolimus era: Evidence of pervasive chronic injury. Am J Transplant. 2018;18:180–188.
Cockfield SM, Wilson S, Campbell PM, et al. Comparison of the effects of standard vs low-dose prolonged-release tacrolimus with or without ACEi/ARB on the histology and function of renal allografts. Am J Transplant. 2019;19:1730–1744.
Wojciechowski D, Wiseman A. Long-term immunosuppression management: opportunities and uncertainties. Clin J Am Soc Nephrol. 2021;16:1264–1271.
van Sandwijk MS, de Vries APJ, Bakker SJL, et al. Early steroid withdrawal compared with standard immunosuppression in kidney transplantation - interim analysis of the Amsterdam-Leiden-Groningen randomized controlled trial. Transplant Direct. 2018;4:e354.
Levey AS, Stevens LA, Schmid CH, et al.; CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604–612.
Loupy A, Haas M, Roufosse C, et al. The Banff 2019 kidney meeting report (I): updates on and clarification of criteria for T cell- and antibody-mediated rejection. Am J Transplant. 2020;20:2318–2331.
Wisse BW, Kamburova EG, Joosten I, et al. Toward a sensible single-antigen bead cutoff based on kidney graft survival. Transplantation. 2019;103:789–797.
Laftavi MR, Stephan R, Stefanick B, et al. Randomized prospective trial of early steroid withdrawal compared with low-dose steroids in renal transplant recipients using serial protocol biopsies to assess efficacy and safety. Surgery. 2005;137:364–371.
Rostaing L, Cantarovich D, Mourad G, et al.; CARMEN Study Group. Corticosteroid-free immunosuppression with tacrolimus, mycophenolate mofetil, and daclizumab induction in renal transplantation. Transplantation. 2005;79:807–814.
Woodle ES, First MR, Pirsch J, et al.; Astellas Corticosteroid Withdrawal Study Group. A prospective, randomized, double-blind, placebo-controlled multicenter trial comparing early (7 day) corticosteroid cessation versus long-term, low-dose corticosteroid therapy. Ann Surg. 2008;248:564–577.
Krämer BK, Klinger M, Vítko S, et al. Tacrolimus-based, steroid-free regimens in renal transplantation: 3-year follow-up of the ATLAS trial. Transplantation. 2012;94:492–498.
Ponticelli C, Carmellini M, Tisone G, et al. A randomized trial of everolimus and low-dose cyclosporine in renal transplantation: with or without steroids? Transplant Proc. 2014;46:3375–3382.
Mourad G, Glyda M, Albano L, et al.; Advagraf-based immunosuppression regimen examining new onset diabetes mellitus in kidney transplant recipients (ADVANCE) study investigators. Incidence of posttransplantation diabetes mellitus in de novo kidney transplant recipients receiving prolonged-release tacrolimus-based immunosuppression with 2 different corticosteroid minimization strategies: ADVANCE, A randomized controlled trial. Transplantation. 2017;101:1924–1934.
Ahsan N, Hricik D, Matas A, et al. Prednisone withdrawal in kidney transplant recipients on cyclosporine and mycophenolate mofetil--a prospective randomized study. steroid withdrawal study group. Transplantation. 1999;68:1865–1874.
Gulanikar AC, Belitsky P, MacDonald AS, et al. Randomized controlled trial of steroids versus no steroids in stable cyclosporine-treated renal graft recipients. Transplant Proc. 1991;23(1 Pt 2):990–991.
Isoniemi H, Ahonen J, Eklund B, et al. Renal allograft immunosuppression. II. A randomized trial of withdrawal of one drug in triple drug immunosuppression. Transpl Int. 1990;3:121–127.
Lebranchu Y. Comparison of two corticosteroid regimens in combination with CellCept and cyclosporine A for prevention of acute allograft rejection: 12 month results of a double-blind, randomized, multi-center study. M 55002 study group. Transplant Proc. 1999;31:249–250.
Kim HC, Chang KJ, Kwon JK, et al. Long-term results of cyclosporine monotherapy in renal transplantation. Transplant Proc. 1998;30:3539–3540.
Sola E, Alférez MJ, Cabello M, et al. Low-dose and rapid steroid withdrawal in renal transplant patients treated with tacrolimus and mycophenolate mofetil. Transplant Proc. 2002;34:1689–1690.
Pascual J, van Hooff JP, Salmela K, et al. Three-year observational follow-up of a multicenter, randomized trial on tacrolimus-based therapy with withdrawal of steroids or mycophenolate mofetil after renal transplant. Transplantation. 2006;82:55–61.
Smak Gregoor PJ, de Sévaux RG, Ligtenberg G, et al. Withdrawal of cyclosporine or prednisone six months after kidney transplantation in patients on triple drug therapy: a randomized, prospective, multicenter study. J Am Soc Nephrol. 2002;13:1365–1373.
Pascual J, Berger SP, Witzke O, et al.; TRANSFORM Investigators. Everolimus with reduced calcineurin inhibitor exposure in renal transplantation. J Am Soc Nephrol. 2018;29:1979–1991.
Berger SP, Sommerer C, Witzke O, et al.; TRANSFORM Investigators. Two-year outcomes in de novo renal transplant recipients receiving everolimus-facilitated calcineurin inhibitor reduction regimen from the TRANSFORM study. Am J Transplant. 2019;19:3018–3034.
Davis S, Gralla J, Klem P, et al. Lower tacrolimus exposure and time in therapeutic range increase the risk of de novo donor-specific antibodies in the first year of kidney transplantation. Am J Transplant. 2018;18:907–915.
Davis S, Wiebe C, Campbell K, et al. Adequate tacrolimus exposure modulates the impact of HLA class II molecular mismatch: a validation study in an American cohort. Am J Transplant. 2021;21:322–328.
Gold A, Tönshoff B, Döhler B, et al. Association of graft survival with tacrolimus exposure and late intra-patient tacrolimus variability in pediatric and young adult renal transplant recipients-an international CTS registry analysis. Transpl Int. 2020;33:1681–1692.
Knight SR, Morris PJ. Steroid avoidance or withdrawal after renal transplantation increases the risk of acute rejection but decreases cardiovascular risk. A meta-analysis. Transplantation. 2010;89:1–14.
Kasiske BL. Epidemiology of cardiovascular disease after renal transplantation. Transplantation. 2001;72(6 Suppl):S5–S8.
Jardine AG, Fellström B, Logan JO, et al. Cardiovascular risk and renal transplantation: Post hoc analyses of the assessment of Lescol in renal transplantation (ALERT) study. Am J Kidney Dis. 2005;46:529–536.
Nair SS, Lenihan CR, Montez-Rath ME, et al. Temporal trends in the incidence, treatment and outcomes of hip fracture after first kidney transplantation in the united states. Am J Transplant. 2014;14:943–951.
Nikkel LE, Mohan S, Zhang A, et al. Reduced fracture risk with early corticosteroid withdrawal after kidney transplant. Am J Transplant. 2012;12:649–659.