Micro RNA 146a-5p expression in Kidney transplant recipients with delayed graft function

ABSTRACT Introduction: The development of novel non-invasive biomarkers of kidney graft dysfunction, especially in the course of the delayed graft function period would be an important step forward in the clinical practice of kidney transplantation. Methods: We evaluated by RT-PCR the expression of miRNA-146 to -5p ribonucleic micro-acids (miRNAs) in the peripheral blood and renal tissue obtained from kidney transplant recipients who underwent a surveillance graft biopsy during the period of delayed graft function. Results: In biopsy samples, the expression of miR-146a-5p was significantly increased in the group of patients with delayed graft function (DGF) (n = 33) versus stables patients (STA) (n = 13) and patients with acute rejection (AR) (n = 9) (p = 0.008). In peripheral blood samples, a non-significant increase of miR-146a-5p expression was found in the DGF group versus STA and AR groups (p = 0.083). No significant correlation was found between levels of expression in biopsy and plasma. ROC curve analysis revealed an AUC of 0.75 (95% CI: 0.62-0.88) for the renal tissue expression and 0.67 (95% CI 0.52-0.81) for the peripheral blood expression. Conclusion: We conclude that miR-146a-5p expression has a distinct pattern in the renal tissue and perhaps in the peripheral blood in the setting of DGF. Further refinements and strategies for studies should be developed in the field of non-invasive molecular diagnosis of kidney graft dysfunction.

摘要 引言：开发新型肾移植功能障碍无创生物标志物，尤其是针对延迟移植功能恢复（delayed graft function, DGF）阶段，将是肾移植临床实践领域的重要突破。方法：本研究通过逆转录聚合酶链式反应（Reverse Transcription-Polymerase Chain Reaction, RT-PCR），检测了延迟移植功能恢复阶段接受移植肾监测活检的肾移植受者外周血与肾组织中miRNA-146至-5p类微小核糖核酸（microRNA, miRNAs）的表达水平。结果：活检样本中，延迟移植功能恢复组（DGF，n=33）患者的miR-146a-5p表达水平显著高于稳定组（stable patients, STA，n=13）与急性排斥反应组（acute rejection, AR，n=9）（p=0.008）。在外周血样本中，DGF组患者的miR-146a-5p表达水平虽有升高，但与STA组及AR组相比无统计学差异（p=0.083）。活检组织与血浆中的miR-146a-5p表达水平未发现显著相关性。受试者工作特征曲线（Receiver Operating Characteristic curve, ROC）分析显示，肾组织中该指标表达的曲线下面积（Area Under Curve, AUC）为0.75（95%置信区间：0.62-0.88），外周血中该指标表达的AUC为0.67（95%置信区间：0.52-0.81）。结论：本研究表明，在延迟移植功能恢复的临床场景中，miR-146a-5p在肾组织中的表达具有独特模式，在外周血中或亦存在此种特征。未来需在肾移植功能障碍无创分子诊断领域，进一步优化研究方案与策略。