早期远程缺血预处理可改善活体供肾移植后移植物功能：移植中肾保护对抗缺血再灌注（REPAIR）随机试验的长期结果。

Early remote ischaemic preconditioning leads to sustained improvement in allograft function after live donor kidney transplantation: long-term outcomes in the REnal Protection Against Ischaemia-Reperfusion in transplantation (REPAIR) randomised trial.

机构信息

Wessex Kidney Centre, Portsmouth Hospitals NHS Trust, Portsmouth, Hampshire, UK; Research and Development, University Hospital Southampton NHS Foundation Trust, Southampton, Hampshire, UK.

Clinical Trials Unit, London School of Hygiene and Tropical Medicine, London, UK.

出版信息

Br J Anaesth. 2019 Nov;123(5):584-591. doi: 10.1016/j.bja.2019.07.019. Epub 2019 Sep 11.

DOI:10.1016/j.bja.2019.07.019

PMID:31521337

Abstract

BACKGROUND

The REnal Protection Against Ischaemia-Reperfusion in transplantation (REPAIR) RCT examined whether remote ischaemic preconditioning (RIPC) improved renal function after living-donor kidney transplantation. The primary endpoint, glomerular filtration rate (GFR), quantified by iohexol at 12 months, suggested that RIPC may confer longer-term benefit. Here, we present yearly follow-up data of estimated GFR for up to 5 yr after transplantation.

METHODS

In this double-blind, factorial RCT, we enrolled 406 adult live donor kidney transplant donor-recipient pairs in 15 European transplant centres. RIPC was performed before induction of anaesthesia. RIPC consisted of four 5 min inflations of a BP cuff on the upper arm to 40 mm Hg above systolic BP separated by 5 min periods of cuff deflation. For sham RIPC, cuff inflation to 40 mm Hg was undertaken. Pairs were randomised to sham RIPC, early RIPC only (immediately pre-surgery), late RIPC only (24 h pre-surgery), or dual RIPC (early and late RIPC). The pre-specified secondary outcome of estimated GFR (eGFR) was calculated from serum creatinine measurements, using the Chronic Kidney Disease Epidemiology Collaboration equation. Predefined safety outcomes were mortality and graft loss.

RESULTS

There was a sustained improvement in eGFR after early RIPC, compared with control from 3 months to 5 yr (adjusted mean difference: 4.71 ml min (1.73 m) [95% confidence interval, CI: 1.54-7.89]; P=0.004). Mortality and graft loss were similar between groups (RIPC: 20/205 [9.8%] vs control 24/201 [11.9%]; hazard ratio: 0.79 [95% CI: 0.43-1.43]).

CONCLUSIONS

RIPC safely improves long-term kidney function after living-donor renal transplantation when administered before induction of anaesthesia.

CLINICAL TRIAL REGISTRATION

ISRCTN30083294.

摘要

背景

REnal Protection Against Ischaemia-Reperfusion in transplantation（REPAIR）RCT 研究了远程缺血预处理（RIPC）是否能改善活体供肾移植后的肾功能。主要终点肾小球滤过率（GFR），在 12 个月时通过 iohexol 定量，表明 RIPC 可能带来更长期的益处。在这里，我们提供了移植后长达 5 年的每年随访估计 GFR 数据。

方法

在这项双盲、析因 RCT 中，我们在 15 个欧洲移植中心招募了 406 对成年活体供肾移植供受者。RIPC 在诱导麻醉前进行。RIPC 由 4 次 5 分钟的上臂袖带充气至收缩压以上 40mmHg 组成，充气间隔为 5 分钟袖带放气期。对于假 RIPC，充气至 40mmHg。将配对随机分为假 RIPC、仅早期 RIPC（手术前即刻）、仅晚期 RIPC（手术前 24 小时）或双重 RIPC（早期和晚期 RIPC）。使用慢性肾脏病流行病学合作（Chronic Kidney Disease Epidemiology Collaboration，CKD-EPI）方程从血清肌酐测量值中计算预先指定的次要结局估计肾小球滤过率（eGFR）。预先定义的安全性结局是死亡率和移植物丢失。

结果

与对照组相比，早期 RIPC 后 eGFR 持续改善，从 3 个月到 5 年（调整平均差异：4.71ml/min（1.73m）[95%置信区间，CI：1.54-7.89]；P=0.004）。各组死亡率和移植物丢失相似（RIPC：20/205[9.8%]vs 对照组 24/201[11.9%]；危险比：0.79[95%CI：0.43-1.43]）。