McGuinness Dagmara, Leierer Johannes, Shapter Olivier, Mohammed Suhaib, Gingell-Littlejohn Marc, Kingsmore David B, Little Ann-Margaret, Kerschbaum Julia, Schneeberger Stefan, Maglione Manuel, Nadalin Silvio, Wagner Sylvia, Königsrainer Alfred, Aitken Emma, Whalen Henry, Clancy Marc, McConnachie Alex, Koppelstaetter Christian, Stevenson Karen S, Shiels Paul G
University of Glasgow, College of Medical, Veterinary & Life Sciences, Wolfson Wohl Translational Research Centre, Institute of Cancer Sciences, Garscube Estate, Switchback Road, Glasgow, G61 1QH, Scotland.
Department of Internal Medicine IV (Nephrology and Hypertension), A-6020 Medical University Innsbruck, Austria.
PLoS One. 2016 Jan 6;11(1):e0146378. doi: 10.1371/journal.pone.0146378. eCollection 2016.
Delayed graft function is a prevalent clinical problem in renal transplantation for which there is no objective system to predict occurrence in advance. It can result in a significant increase in the necessity for hospitalisation post-transplant and is a significant risk factor for other post-transplant complications.
The importance of microRNAs (miRNAs), a specific subclass of small RNA, have been clearly demonstrated to influence many pathways in health and disease. To investigate the influence of miRNAs on renal allograft performance post-transplant, the expression of a panel of miRNAs in pre-transplant renal biopsies was measured using qPCR. Expression was then related to clinical parameters and outcomes in two independent renal transplant cohorts.
Here we demonstrate, in two independent cohorts of pre-implantation human renal allograft biopsies, that a novel pre-transplant renal performance scoring system (GRPSS), can determine the occurrence of DGF with a high sensitivity (>90%) and specificity (>60%) for donor allografts pre-transplant, using just three senescence associated microRNAs combined with donor age and type of organ donation.
These results demonstrate a relationship between pre-transplant microRNA expression levels, cellular biological ageing pathways and clinical outcomes for renal transplantation. They provide for a simple, rapid quantitative molecular pre-transplant assay to determine post-transplant allograft function and scope for future intervention. Furthermore, these results demonstrate the involvement of senescence pathways in ischaemic injury during the organ transplantation process and an indication of accelerated bio-ageing as a consequence of both warm and cold ischaemia.
移植肾功能延迟是肾移植中普遍存在的临床问题，目前尚无客观系统可提前预测其发生。它会导致移植后住院必要性显著增加，并且是其他移植后并发症的重要危险因素。
微小RNA（miRNA）作为小RNA的一个特定亚类，其重要性已被明确证明会影响健康和疾病中的许多途径。为了研究miRNA对移植后肾移植性能的影响，使用qPCR测量了移植前肾活检中一组miRNA的表达。然后将表达与两个独立肾移植队列中的临床参数和结果相关联。
在此，我们在两个独立的植入前人类肾移植活检队列中证明，一种新型的移植前肾功能评分系统（GRPSS），仅使用三种与衰老相关的微小RNA结合供体年龄和器官捐赠类型，就可以对移植前的供体同种异体移植物以高灵敏度（>90%）和特异性（>60%）确定移植肾功能延迟的发生。
这些结果证明了移植前微小RNA表达水平、细胞生物学衰老途径与肾移植临床结果之间的关系。它们提供了一种简单、快速的定量分子移植前检测方法，以确定移植后同种异体移植物功能和未来干预的范围。此外，这些结果证明了衰老途径在器官移植过程中的缺血性损伤中的参与，以及温暖和寒冷缺血导致生物衰老加速的迹象。
