A Five-Year Prospective, Randomized, Open-Label Study of Standard-Dose Versus Low-Dose Prolonged-Release Tacrolimus With or Without Angiotensin-Converting Enzyme Inhibitor or Angiotensin II Receptor Blocker Post Kidney Transplantation.

Autor: Campbell PM; Department of Laboratory Medicine and Pathology, University of Alberta Hospitals, Edmonton, Alberta, Canada., Cantarovich M; Division of Nephrology, Department of Medicine, McGill University Health Centre, Montréal, Québec, Canada., Gangji A; Department of Medicine, St Joseph's Healthcare Hamilton, Hamilton, Ontario, Canada., Houde I; Department of Medicine, L'Hôtel-Dieu de Québec, Québec City, Québec, Canada., Jevnikar AM; Department of Internal Medicine, London Health Sciences Centre, London, Ontario, Canada., Monroy-Cuadros FM; Division of Transplant Surgery, Foothills Medical Centre, Calgary, Alberta, Canada., Nickerson PW; Department of Internal Medicine and Immunology, Health Sciences Centre, Winnipeg, Manitoba, Canada., Pâquet MR; Division of Nephrology, Hôpital Notre-Dame du CHUM, Montréal, Québec, Canada., Prasad GVR; Division of Nephrology, St Michael's Hospital, Toronto, Ontario, Canada., Senécal L; Department of Medicine, Hôpital Maisonneuve-Rosemont, Montréal, Québec, Canada., Wolff JL; Department of Medicine, Centre Hospitalier Universitaire, Sherbrooke, Québec, Canada., Schwartz JJ; Medical Affairs, Astellas Pharma Global Development, Northbrook, Illinois, USA., Rush DN; Department of Internal Medicine and Immunology, Health Sciences Centre, Winnipeg, Manitoba, Canada.
Jazyk: angličtina
Zdroj: Clinical transplantation [Clin Transplant] 2025 Jan; Vol. 39 (1), pp. e70067.
DOI: 10.1111/ctr.70067
Abstrakt: Introduction: Novel approaches to improve long-term outcomes in kidney transplant recipients are required. Here, we present the 5-year data from a multicenter, prospective, Phase 3b trial evaluating treatment outcomes with standard (STD) or low (LOW) dose prolonged-release tacrolimus (TAC) combined with ACEi/ARB or other antihypertensive therapy (OAHT) in Canadian kidney transplant recipients.
Methods: Adult de novo kidney transplant recipients were randomized 2 × 2 to STD or LOW dose TAC and ACEi/ARB or OAHT. Patients had received a first or second transplant from a living or deceased donor and had ≥ 1 human leukocyte antigen mismatch with their donor.
Results: There were 281 patients from 13 sites across Canada. Overall patient survival was 95.7% and was comparable between groups. Graft survival at study end was 89.7% in the LOW+OAHT group and 94.4%-97.1% in the other groups and BPAR, and Class II de novo donor-specific antibodies (dnDSA) were higher in the LOW+OAHT group than in the other groups. However, these differences were not statistically significant. Graft function, blood pressure (BP), and proteinuria were similar between the groups; however, between 2 and 5 years there was a 2-fold or greater increase in the use of ACEi/ARB in patients randomized initially to OAHT, mostly because of hypertension and proteinuria. There were no unexpected safety findings.
Conclusion: Patients randomized to LOW TAC with renin-angiotensin system (RAS) blockade had similar outcomes at 5 years as patients treated with STD TAC with or without RAS blockade, whereas those randomized to LOW TAC without RAS blockade showed a non-significant trend towards more rejections and dnDSA TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00933231.
(© 2024 The Author(s). Clinical Transplantation published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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