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ABO 不相容肾移植后的临床结局:系统评价和荟萃分析。

Clinical outcomes after ABO-incompatible renal transplantation: a systematic review and meta-analysis.

机构信息

Clinic of Nephrology and Hypertension, Diabetology and Endocrinology, Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany.

Clinic of Nephrology and Hypertension, Diabetology and Endocrinology, Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany.

出版信息

Lancet. 2019 May 18;393(10185):2059-2072. doi: 10.1016/S0140-6736(18)32091-9. Epub 2019 Apr 18.

Abstract

BACKGROUND

ABO-incompatible renal transplantation (ABOi-rTx) is increasingly used to overcome organ shortage. Evidence about its non-inferiority in comparison with ABO-compatible renal transplantation (ABOc-rTx) needs to be analysed at early and late timepoints. We aimed to investigate differences in outcome after ABOi-rTX and ABOc-rTX.

METHODS

We did a systematic review and meta-analysis of observational studies published up until Dec 31, 2017, that reported outcome data (≥1 year of follow-up) after ABOi-rTx and included an ABO-compatible control group, by searching the Cochrane Central Register of Controlled Trials (CENTRAL), Embase Ovid, MEDLINE Ovid, and PubMed. Trials on recipients of ABOi-rTx were assessed, if an ABO-compatible control group was included and if outcome data on at least graft or recipient survival with 1 year or more of follow-up were available. Exclusion criteria included case reports, editorials, reviews and letters, animal studies, meeting papers, studies unable to extract data, non-renal solid organ and bone-marrow transplant studies, and deceased donor ABOc-rTx. Data were extracted from published reports. Primary endpoints were all-cause mortality and graft survival at 1, 3, 5, and more than 8 years after transplantation. In the meta-analysis, we used a fixed-effects model if the I value was 0, and both a fixed-effects and random-effects model if I was more than 0. This study is registered with PROSPERO, number CRD42018094550.

FINDINGS

1264 studies were screened and 40 studies including 49 patient groups were identified. 65 063 patients were eligible for analysis, 7098 of whom had undergone ABOi-rTx. Compared with ABOc-rTx, ABOi-rTx was associated with significantly higher 1-year mortality (odds ratio [OR] 2·17 [95% CI 1·63-2·90], p<0·0001; I=37%), 3 years (OR 1·89 [1·46-2·45], p<0·0001; I=29%), and 5 years (OR 1·47 [1·08-2·00], p=0·010; I=68%) following transplantation. Death-censored graft survival was lower with ABOi-rTx than with ABOc-rTx at 1 year (OR 2·52 [1·80-3·54], p<0·0001; I=61%) and 3 years (OR 1·59 [1·15-2·18], p=0·0040; I=58%) only. Graft losses were equivalent to that of ABOc-rTx after 5 years and patient survival after 8 years. No publication bias was detected and the results were robust to trial sequential analysis until 5 years after transplantation; thereafter, data became futile or inconclusive.

INTERPRETATION

Despite progress in desensitisation protocols and optimisation of ABOi-rTx procedures, excess mortality and loss of kidney grafts was found compared with ABOc-rTx within the first 3 years after transplantation. Only long-term outcomes after 5 years yielded equivalent survival rates and organ function. Awareness of the increased risks of infection, organ rejection, and bleeding could improve care of patients and promote efforts towards paired kidney exchange programmes.

FUNDING

None.

摘要

背景

ABO 血型不相容的肾移植(ABOi-rTx)越来越多地被用于克服器官短缺的问题。与 ABO 血型相容的肾移植(ABOc-rTx)相比,需要分析其在早期和晚期的非劣效性。我们旨在调查 ABOi-rTx 和 ABOc-rTx 后结果的差异。

方法

我们对截至 2017 年 12 月 31 日发表的观察性研究进行了系统评价和荟萃分析,这些研究报告了 ABOi-rTx 后(随访时间≥1 年)的结果数据,并纳入了 ABO 相容的对照组,通过搜索 Cochrane 中央对照试验注册库(CENTRAL)、Embase Ovid、MEDLINE Ovid 和 PubMed 进行检索。如果纳入了 ABO 相容的对照组,并且有至少 1 年或更长时间的移植物或受者存活率的结果数据,则评估了接受 ABOi-rTx 的受者试验。排除标准包括病例报告、社论、评论和信件、动物研究、会议论文、无法提取数据的研究、非肾脏实体器官和骨髓移植研究以及已故供体 ABOc-rTx。从已发表的报告中提取数据。主要终点是移植后 1、3、5 年及以上的全因死亡率和移植物存活率。在荟萃分析中,如果 I 值为 0,则使用固定效应模型,如果 I 值大于 0,则同时使用固定效应和随机效应模型。本研究在 PROSPERO 注册,编号为 CRD42018094550。

发现

筛选了 1264 篇研究,确定了 40 项研究,包括 49 个患者组。65063 名患者符合分析条件,其中 7098 名患者接受了 ABOi-rTx。与 ABOc-rTx 相比,ABOi-rTx 与 1 年(比值比[OR]2.17[95%CI 1.63-2.90],p<0.0001;I=37%)、3 年(OR 1.89[1.46-2.45],p<0.0001;I=29%)和 5 年(OR 1.47[1.08-2.00],p=0.010;I=68%)后死亡率显著增加。与 ABOc-rTx 相比,ABOi-rTx 1 年(OR 2.52[1.80-3.54],p<0.0001;I=61%)和 3 年(OR 1.59[1.15-2.18],p=0.0040;I=58%)的死亡校正移植物存活率较低。5 年后移植物丢失率与 ABOc-rTx 相当,8 年后患者存活率与 ABOc-rTx 相当。未发现发表偏倚,结果在移植后 5 年内进行了试验序贯分析是稳健的;此后,数据变得无效或不确定。

解释

尽管在脱敏方案和优化 ABOi-rTx 程序方面取得了进展,但与 ABOc-rTx 相比,移植后前 3 年内仍发现死亡率和肾脏移植物丢失增加。只有 5 年后的长期结果才能产生等效的存活率和器官功能。了解感染、器官排斥和出血的风险增加可以改善患者的护理,并促进配对肾脏交换计划的努力。

资金

无。

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