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A circulating exosomal microRNA panel as a novel biomarker for monitoring post‐transplant renal graft function

机译:一种循环外泌体MicroRNA面板作为一种用于监测移植后肾移植功能的新型生物标志物

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摘要

Accurate and effective biomarkers for continuous monitoring of graft function are needed after kidney transplantation. The aim of this study was to establish a circulating exosomal miRNA panel as non‐invasive biomarker for kidney transplant recipients. Plasma exosomes of 58 kidney transplant recipients and 27 healthy controls were extracted by gel exclusion chromatography and characterized by transmission electron microscopy, nanoparticle tracking analysis and Western blotting. Post‐transplant renal graft function was evaluated by estimated glomerular filtration rate (eGFR). Quantitative real‐time polymerase chain reaction was used to determine the expression of exosomal microRNAs (miRNAs). Exosomal miR‐21, miR‐210 and miR‐4639 showed negative correlations with eGFR in the training set and were selected for further analysis. In the validation set, miR‐21, miR‐210 and miR‐4639 showed the capability to discriminate between subjects with chronic allograft dysfunction (eGFR < 60 mL/min/1.73 m2) and those with normal graft function (eGFR > 90 mL/min/1.73 m2). Three‐miRNA panel exhibited higher accuracy compared with individual miRNAs or double indicators. One‐year follow‐up revealed a stable recovery of allograft function in subjects with low calculated score from three‐miRNA panel (below the optimal cut‐off value). In conclusion, a unique circulating exosomal miRNA panel was identified as an effective biomarker for monitoring post‐transplant renal graft function in this study.
机译:在肾移植后需要准确和有效的生物标志物,用于连续监测接枝功能。本研究的目的是建立一个循环外泌体miRNA小组,作为肾移植受者的非侵入性生物标志物。通过凝胶排阻色谱法提取58个肾移植受体和27个健康对照的血浆外来,并通过透射电子显微镜,纳米粒子跟踪分析和蛋白质印迹。通过估计的肾小球过滤速率(EGFR)评估移植后肾移植功能。定量实时聚合酶链反应用于确定外泌体microRNA(miRNA)的表达。外泌体miR-21,miR-210和miR-4639显示出与训练集中的EGFR的负相关性,并选择进一步分析。在验证集中,MIR-21,MIR-210和MIR-4639显示了慢性同种异体移植功能障碍(EGFR <60ml / min / 1.73m 2)的受试者的能力,具有正常接枝函数(EGFR> 90ml / Min / 1.73 M2)。与单独的miRNA或双指标相比,三分之一的面板表现出更高的准确性。一年的后续随访揭示了从三MiRNA面板的低计算得分(低于最佳截止值)的对象中同种异体移植函数的稳定恢复。总之,鉴定了一种独特的循环外泌体miRNA小组作为监测本研究中移植后肾移植功能的有效生物标志物。

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