Background

Islet transplantation has been associated with better metabolic control and quality of life than insulin treatment alone, but direct evidence of its effect on hard clinical endpoints is scarce. We aimed to assess the effect of islet transplantation on patient-graft survival in kidney transplant recipients with type 1 diabetes.

Methods

In this retrospective cohort study, we enrolled all patients with type 1 diabetes who received a kidney graft in France during the study period, identified from the CRISTAL nationwide registry. Non-inclusion criteria included recipients from transplant centres that never proposed islet transplantation during the study period, recipients with a functional pancreas throughout the follow-up duration, recipients with more than two kidney transplants, HLA-sensitised recipients, recipients with less than 1 year of follow-up after kidney transplantation, misclassified recipients with type 2 diabetes, recipients aged over 65 years, recipients of kidney grafts from Donation after Circulatory Death donors, recipient with HIV or hepatitis, recipients with cancer, and recipients of combined liver-kidney transplants. Patients who also received islet-after-kidney (IAK) transplantation were compared with controls who received kidney transplantation alone according to a 1:2 matching method based on time-dependent propensity scores, ensuring patients comparability at the time of islet transplantation. The primary outcome was patient-graft survival, a composite outcome defined by death, re-transplantation, or return to dialysis.

Findings

Between Jan 1, 2000, and Dec 31, 2017, 2391 patients with type 1 diabetes were identified as having received a kidney transplant, 47 patients of whom also received an islet transplantation. 2002 patients were not eligible for islet transplantation and 62 were excluded due to missing data. 327 eligible recipients from 15 centres were included in the study dataset for the target trial emulation. 40 patients who received IAK transplantation were successfully matched to 80 patients who received kidney transplantation alone. 13 (33%) of 40 patients in the IAK transplantation group returned to dialysis or died, compared with 36 (45%) of 80 patients in the kidney transplantation alone group. We found a significant benefit of islet transplantation compared with kidney transplantation alone on patient-graft survival, with a hazard ratio (HR) of 0·44 (95% CI 0·23–0·88; p=0·022), mainly explained by a protective effect on the risk of death (HR 0·41, 0·13–0·91; p=0·042). There was no meaningful association between IAK and death-censored graft survival (0·73, 0·30–1·89; p=0·36).

Interpretation

In kidney transplant recipients with type 1 diabetes, IAK transplantation was associated with a significantly better patient-graft survival compared with kidney transplantation alone, mainly due to a protective effect on the risk of death. These results potentially serve as compelling grounds for advocating wider access to islet transplantation in patients with type 1 diabetes undergoing kidney transplant, as reimbursement of islet transplantation is provided in few countries worldwide.

Funding

Programme Hospitalier de la Recherche Clinique, Fondation pour la Recherche Medicale, and Fonds de Dotation Line Renaud-Loulou Gasté.

中文翻译：

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1 型糖尿病肾移植受者肾移植后胰岛与单肾移植 （KAIAK）：法国一项基于人群的靶向试验模拟

 背景

与单独胰岛素治疗相比，胰岛移植与更好的代谢控制和生活质量相关，但其对硬性临床终点影响的直接证据很少。我们旨在评估胰岛移植对 1 型糖尿病肾移植受者患者移植物存活率的影响。

 方法

在这项回顾性队列研究中，我们招募了研究期间在法国接受肾移植的所有 1 型糖尿病患者，这些患者是从 CRISTAL 全国登记处确定的。非纳入标准包括来自移植中心但在研究期间从未提出胰岛移植的受者、在整个随访期间胰腺功能正常的受者、两次以上肾移植的受者、HLA 致敏受者、肾移植后随访少于 1 年的受者、错误分类的 2 型糖尿病受者、年龄超过 65 岁的受者， 循环死亡后捐献供体的肾移植物受者、HIV 或肝炎受者、癌症受者以及肝肾联合移植受者。根据基于时间依赖性倾向评分的 1：2 匹配方法，将同时接受肾后胰岛 （IAK） 移植的患者与单独接受肾移植的对照组进行比较，确保患者在胰岛移植时的可比性。主要结局是患者移植物存活率，这是一种定义为死亡、再移植或恢复透析的复合结局。

 发现

在 2000 年 1 月 1 日至 2017 年 12 月 31 日期间，2391 名 1 型糖尿病患者被确定接受了肾移植，其中 47 名患者还接受了胰岛移植。2002 例患者不符合胰岛移植条件，62 例因数据缺失而被排除在外。来自 15 个中心的 327 名符合条件的受者被纳入目标试验模拟的研究数据集中。40 例接受 IAK 移植的患者与 80 例单独接受肾移植的患者成功匹配。IAK 移植组 40 例患者中有 13 例 （33%） 恢复透析或死亡，而单独肾移植组 80 例患者中有 36 例 （45%） 复发或死亡。我们发现，与单独肾移植相比，胰岛移植对患者移植物生存率有显著益处，风险比 （HR） 为 0·44 （95% CI 0·23–0·88;p=0·022），主要由对死亡风险的保护作用解释 （HR 0·41， 0·13–0·91;p=0·042）。IAK 与死亡删失缺失移植物存活率之间没有有意义的关联 （0·73， 0·30–1·89;p=0·36）。

 解释

在患有 1 型糖尿病的肾移植受者中，与单独肾移植相比，IAK 移植与显着更好的患者移植物存活率相关，主要是由于对死亡风险的保护作用。这些结果可能成为倡导在接受肾移植的 1 型糖尿病患者中更广泛地获得胰岛移植的令人信服的理由，因为全球少数国家提供胰岛移植的报销。

 资金

医院临床研究计划、医学研究基金会和 Line Renaud-Loulou Gasté 捐赠基金。