**1. Introduction**

Acute rejection (AR) is considered to be a prominent cause of graft failure in the first year after transplantation in kidney transplant recipients [1,2], although the long-term consequences of AR remain a subject of discussion. Despite better screening and improved immune suppressive therapies, rejection is still suspected to cause a significant proportion of death censored graft failure after kidney transplantation [3,4]. Previous research showed a prolonged effect on kidney function deterioration as well as graft survival after a rejection episode [2]. Microvascular endothelial cells (ECs) are very susceptible to injury, that can result from episodes of AR. Following the alloimmune response, cytokines and growth factors are produced that can lead to EC activation and microvascular destabilization [5–10]. These rejection-associated events can result in perpetual EC damage and promotion of (aberrant) angiogenesis within the allograft [5,7,9]. Together, these insults can lead to the loss of the microvasculature, chronic ischemia and cell death [11,12], and ultimately, to the development of interstitial fibrosis/tubular atrophy and graft dysfunction [5,6,9]. Therefore, monitoring the course of microvascular injury after rejection could be beneficial in deciding on the best treatment strategies. Previously, we found the vascular injury markers soluble thrombomodulin (sTM) and Angiopoietin-2 (Ang-2) to increase upon AR. sTM normalized in the first year after AR, while Ang-2 remained elevated [13]. Noncoding RNA, such as micro RNAs (miRNA) and long noncoding RNAs (lncRNA)are increasingly recognized to play an important role in vascular injury [14]. The functions of lncRNAs appear to be very diverse as they can bind DNA, proteins, and other RNAs. E.g. lncRNAs have been demonstrated to serve as a scaffold for transcription factors or can assist chromatin-modifying enzymes, thereby regulating gene expression [15]. LncRNAs were also found to be important for miRNA processing, (alternative) splicing, translation and post-transcriptional regulation, for instance via sponging miRNAs [16,17]. In addition, lncRNAs can be promising biomarkers in a variety of vascular diseases and kidney injury [14,16]. Furthermore, lncRNAs have previously been associated with AR [18], but their dynamics after rejection have not been studied before. Earlier, we described that specific lncRNAs (MALAT1, LNC-RPS24, LNC-EPHA6, and LIPCAR) associate with microvascular damage and angiogenic factors in patients with diabetic nephropathy that received simultaneous kidney-pancreas transplantation [19], but their relation with AR and associated vascular damage is unclear. As such, in this study we first explored the relation of AR with local microvascular injury. Then, in a cross-sectional study of patients with T cell mediated AR, we analyzed selected vascular injury related lncRNAs as potential biomarkers for vascular damage in the context of kidney transplant rejection and assess the dynamics in these lncRNAs after rejection.
