Campbell Patricia M, Cantarovich Marcelo, Gangji Azim, Houde Isabelle, Jevnikar Anthony M, Monroy-Cuadros Felix-Mauricio, Nickerson Peter W, Pâquet Michel R, Prasad G V Ramesh, Senécal Lynne, Wolff Jean-Luc, Schwartz Jason J, Rush David N
Department of Laboratory Medicine and Pathology, University of Alberta Hospitals, Edmonton, Alberta, Canada.
Division of Nephrology, Department of Medicine, McGill University Health Centre, Montréal, Québec, Canada.
Clin Transplant. 2025 Jan;39(1):e70067. doi: 10.1111/ctr.70067.
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.
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.
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.
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.
需要新的方法来改善肾移植受者的长期预后。在此，我们展示了一项多中心、前瞻性3b期试验的5年数据，该试验评估了加拿大肾移植受者使用标准（STD）或低（LOW）剂量缓释他克莫司（TAC）联合ACEi/ARB或其他抗高血压治疗（OAHT）的治疗效果。
成年初发肾移植受者按2×2随机分组，接受STD或LOW剂量TAC以及ACEi/ARB或OAHT治疗。患者接受了来自活体或 deceased 供体的首次或第二次移植，且与供体的人类白细胞抗原错配≥1个。
来自加拿大13个地点的281名患者参与了研究。总体患者生存率为95.7%，各治疗组之间相当。研究结束时，LOW+OAHT组的移植物生存率为89.7%，其他组为94.4%-97.1%，LOW+OAHT组的BPAR和II类初发供体特异性抗体（dnDSA）高于其他组。然而，这些差异无统计学意义。各治疗组之间的移植物功能、血压（BP）和蛋白尿情况相似；但是，在最初随机分配至OAHT组的患者中，2至5年间ACEi/ARB的使用增加了2倍或更多，主要原因是高血压和蛋白尿。未发现意外的安全性问题。
随机接受低剂量TAC联合肾素-血管紧张素系统（RAS）阻断治疗的患者在5年时的预后与接受标准剂量TAC联合或不联合RAS阻断治疗的患者相似，而随机接受低剂量TAC但未联合RAS阻断治疗的患者出现更多排斥反应和dnDSA的趋势不显著。试验注册：ClinicalTrials.gov标识符：NCT00933231。
