Remote ischaemic conditioning (RIC) is currently being explored as a non-invasive method to attenuate ischaemia/reperfusion injuries in organs. A randomised clinical study (CONTEXT) evaluated the effects of RIC compared to non-RIC controls in human kidney transplants. RIC was induced prior to kidney reperfusion by episodes of obstruction to arterial flow in the leg opposite the transplant using a tourniquet (4 × 5 min). Although RIC did not lead to clinical improvement of transplant outcomes, we explored whether RIC induced molecular changes through precision analysis of CONTEXT recipient plasma and kidney tissue samples by high-resolution tandem mass spectrometry (MS/MS). We observed an accumulation of muscle derived proteins and altered amino acid metabolism in kidney tissue proteomes, likely provoked by RIC, which was not reflected in plasma. In addition, MS/MS analysis demonstrated transient upregulation of several acute phase response proteins (SAA1, SAA2, CRP) in plasma, 1 and 5 days post-transplant in RIC and non-RIC conditions with a variable effect on the magnitude of acute inflammation. Together, our results indicate sub-clinical systemic and organ-localised effects of RIC.

中文翻译：

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定量蛋白质组学揭示了远程缺血调节在人肾移植中的亚临床作用

远程缺血调节（RIC）当前正在作为一种非侵入性方法来减轻器官的局部缺血/再灌注损伤。一项随机临床研究（CONTEXT）评估了RIC与非RIC对照在人肾移植中的作用。肾再灌注之前，使用止血带（4×5分钟）在移植物对侧腿部阻塞动脉血流，从而诱发了RIC。尽管RIC并未导致移植结果的临床改善，但我们通过RICDS高分辨率串联质谱（MS / MS），通过对TEXT受体血浆和肾脏组织样品的精确分析，探讨了RIC是否诱导了分子变化。我们观察到肾脏组织蛋白质组中肌肉衍生蛋白质的积累和氨基酸代谢的改变，这可能是由R​​IC引起的，而血浆中并未反映出这种情况。此外，MS / MS分析表明，在RIC和非RIC条件下，移植后1天和5天，血浆中几种急性期反应蛋白（SAA1，SAA2，CRP）瞬时上调，对急性炎症的程度有不同的影响。在一起，我们的结果表明RIC的亚临床全身和器官局部作用。