新发肾移植受者基于他克莫司的长期缓释免疫抑制治疗：ADVANCE研究中患者的5年前瞻性随访

Long-term Prolonged-release Tacrolimus-based Immunosuppression in De Novo Kidney Transplant Recipients: 5-Y Prospective Follow-up of Patients in the ADVANCE Study.

作者信息

Pernin Vincent, Glyda Maciej, Viklický Ondrej, Lõhmus Aleksander, Wennberg Lars, Witzke Oliver, von Zur-Mühlen Bengt, Anaokar Swapneel, Hurst Martin, Kazeem Gbenga, Undre Nasrullah, Kuypers Dirk R J

机构信息

Department of Nephrology, Dialysis and Transplantation, Hôpital Lapeyronie, University of Montpellier, Montpellier, France.

Department of Transplantology and Surgery, District Public Hospital Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Bydgoszcz, Poland.

出版信息

Transplant Direct. 2023 Feb 8;9(3):e1432. doi: 10.1097/TXD.0000000000001432. eCollection 2023 Mar.

DOI:10.1097/TXD.0000000000001432

PMID:36875940

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9977488/

Abstract

UNLABELLED

Although prolonged-release tacrolimus (PR-T) is widely approved for posttransplantation immunosuppression in kidney recipients, large-scale studies are required to assess long-term outcomes. We present follow-up data from the Advagraf-based Immunosuppression Regimen Examining New Onset Diabetes Mellitus in Kidney Transplant Recipients (ADVANCE) trial, in which kidney transplant patients (KTPs) received corticosteroid minimization with PR-T.

METHODS

ADVANCE was a 24-wk, randomized, open-label, phase-4 study. De novo KTPs received PR-T with basiliximab and mycophenolate mofetil and were randomized to receive an intraoperative corticosteroid bolus plus tapered corticosteroids until day 10 (arm 1) or an intraoperative corticosteroid bolus (arm 2). In this 5-y, noninterventional follow-up, patients received maintenance immunosuppression according to standard practice. The primary endpoint was graft survival (Kaplan-Meier). Secondary endpoints included patient survival, biopsy-confirmed acute rejection-free survival, and estimated glomerular filtration rate (4-variable modification of diet in renal disease).

RESULTS

Follow-up study included 1125 patients. Overall graft survival at 1 and 5 y posttransplantation was 93.8% and 88.1%, respectively, and was similar between treatment arms. At 1 and 5 y, patient survival was 97.8% and 94.4%, respectively. Five-year graft and patient survival rates in KTPs who remained on PR-T were 91.5% and 98.2%, respectively. Cox proportional hazards analysis demonstrated similar risk of graft loss and death between treatment arms. Five-year biopsy-confirmed acute rejection-free survival was 84.1%. Mean ± standard deviation values of estimated glomerular filtration rate were 52.7 ± 19.5 and 51.1 ± 22.4 mL/min/1.73 m at 1 and 5 y, respectively. Fifty adverse drug reactions were recorded, probably tacrolimus-related in 12 patients (1.5%).

CONCLUSIONS

Graft survival and patient survival (overall and for KTPs who remained on PR-T) were numerically high and similar between treatment arms at 5 y posttransplantation.

摘要

未标注

尽管缓释他克莫司（PR-T）已被广泛批准用于肾移植受者的移植后免疫抑制，但仍需要大规模研究来评估长期疗效。我们展示了肾移植受者基于Advagraf的免疫抑制方案研究新发糖尿病（ADVANCE）试验的随访数据，在该试验中，肾移植患者（KTPs）接受了PR-T并尽量减少使用皮质类固醇。

方法

ADVANCE是一项为期24周的随机、开放标签的4期研究。初发KTPs接受PR-T联合巴利昔单抗和霉酚酸酯，并被随机分为接受术中皮质类固醇大剂量注射加逐渐减量的皮质类固醇直至第10天（组1）或术中皮质类固醇大剂量注射（组2）。在这项为期5年的非干预性随访中，患者按照标准做法接受维持免疫抑制治疗。主要终点是移植物存活率（Kaplan-Meier法）。次要终点包括患者存活率、活检证实的无急性排斥反应存活率以及估计肾小球滤过率（肾病饮食的4变量修正法）。

结果

随访研究纳入了1125例患者。移植后1年和5年的总体移植物存活率分别为93.8%和88.1%，各治疗组之间相似。1年和5年时，患者存活率分别为97.8%和94.4%。继续使用PR-T的KTPs的5年移植物和患者存活率分别为91.5%和98.2%。Cox比例风险分析显示各治疗组之间移植物丢失和死亡风险相似。5年活检证实的无急性排斥反应存活率为84.1%。估计肾小球滤过率的平均值±标准差在1年和5年时分别为52.7±19.5和51.1±22.4 mL/min/1.73 m²。记录了50例药物不良反应，其中12例患者（1.5%）可能与他克莫司有关。