The fate of transplanted kidneys is substantially influenced by graft quality, with transplantation of kidneys from elderly and expanded criteria donors (ECDs) associated with higher occurrence of delayed graft function, rejection, and inferior long-term outcomes. However, little is known about early molecular fingerprints of these events in different donor categories. Borderline changes represent the most frequent histological finding early after kidney transplantation. Therefore, we examined outcomes and transcriptomic profiles of early-case biopsies diagnosed as borderline changes in different donor categories. In this single-center, retrospective, observational study, we compared midterm outcomes of kidney transplant recipients with early borderline changes as a first pathology between ECD (n = 109), standard criteria donor (SCDs, n = 109), and living donor (LD, n = 51) cohorts. Intragraft gene expression profiling by microarray was performed in part of these ECD, SCD, and LD cohorts. Although 5 year graft survival in patients with borderline changes in early-case biopsies was not influenced by donor category (log-rank P = 0.293), impaired kidney graft function (estimated glomerular filtration rate by Chronic Kidney Disease Epidemiology Collaboration equation) at M3, 1, 2, and 3 years was observed in the ECD cohort (P < 0.001). Graft biopsies from ECD donors had higher vascular intimal fibrosis and arteriolar hyalinosis compared to SCD and LD (P < 0.001), suggesting chronic vascular changes. Increased transcripts typical for ECD, as compared to both LD and SCD, showed enrichment of the inflammatory, defense, and wounding responses and the ECM–receptor interaction pathway. Additionally, increased transcripts in ECD vs. LD showed activation of complement and coagulation and cytokine–cytokine receptor pathways along with platelet activation and cell cycle regulation. Comparative gene expression overlaps of ECD, SCD, and LD using Venn diagrams found 64 up- and 16 down-regulated genes in ECD compared to both LD and SCD. Shared increased transcripts in ECD vs. both SCD and LD included thrombospondin-2 (THBS2), angiopoietin-like 4 (ANGPTL4), collagens (COL6A3, COL1A1), chemokine CCL13, and interleukin IL11, and most significantly, down-regulated transcripts included proline-rich 35 (PRR35) and fibroblast growth factor 9. Early borderline changes in ECD kidney transplantation are characterized by increased regulation of inflammation, extracellular matrix remodeling, and acute kidney injury transcripts in comparison with both LD and SCD grafts.

移植肾的命运很大程度上受移植物质量的影响，老年人和扩展标准供体（ECD）移植肾会导致移植物功能延迟，排斥反应和长期效果较差的发生率更高。但是，对于这些事件在不同供体类别中的早期分子指纹知之甚少。边界改变代表肾脏移植后早期最常见的组织学发现。因此，我们检查了诊断为不同供体类别的临界变化的早期病例活检的结果和转录组谱。在这项单中心，回顾性，观察性研究中，我们比较了早期肾边界改变作为早期ECD之间的病理变化的肾脏移植接受者的中期结局（ñ = 109），标准标准捐助者（SCD， ñ = 109）和活体捐献者（LD， ñ= 51）同类群组。在这些ECD，SCD和LD队列中，通过微阵列进行了移植物中基因表达谱分析。尽管早期活检的边缘改变患者的5年移植物存活不受捐赠者类别的影响（log-rankP = 0.293），在ECD队列中观察到M3、1、2和3年时肾移植功能受损（通过慢性肾脏病流行病学协作方程估算的肾小球滤过率）（P<0.001）。与SCD和LD相比，ECD供体的移植物活检具有更高的血管内膜纤维化和小动脉透明质化（P<0.001），提示慢性血管变化。与LD和SCD相比，ECD的典型转录本增加，显示出炎症，防御和创伤反应以及ECM-受体相互作用途径的富集。此外，ECD与LD的转录本增加表明补体和凝血以及细胞因子-细胞因子受体途径的活化以及血小板活化和细胞周期调节。使用Venn图，比较ECD，SCD和LD的基因表达重叠，发现与LD和SCD相比，ECD中有64个上调和16个下调的基因。与SCD和LD相比，ECD中共享的转录本增加包括thrombospondin-2（泰铢2），类血管生成素4（ANGPTL4），胶原蛋白（COL6A3，COL1A1），趋化因子 CCL13和白介素 白介素11，最重要的是，下调的转录本包括富含脯氨酸的35（PRR35）和成纤维细胞生长因子9.与LD和SCD移植相比，ECD肾脏移植的早期边界改变的特征是炎症调节增强，细胞外基质重塑和急性肾损伤转录本。