Institute of Molecular and Translational Therapeutic Strategies (IMTTS) Department of Medicine/Division of Nephrology and Hypertension, Hannover Medical School, Hanover, Germany.
Am J Transplant. 2011 Oct;11(10):2221-7. doi: 10.1111/j.1600-6143.2011.03679.x. Epub 2011 Aug 3.
MicroRNAs (miRNAs) are small ribonucleotides regulating gene expression. Circulating miRNAs are remarkably stable in the blood. We tested whether miRNAs are also detectable in urine and may serve as new predictors of outcome in renal transplant patients with acute rejection. We profiled urinary miRNAs of stable transplant patients and transplant patients with acute rejection. The miR-10a, miR-10b and miR-210 were strongly deregulated in urine of the patients with acute rejection. We confirmed these data in urine of a validation cohort of 62 patients with acute rejection, 19 control transplant patients without rejection and 13 stable transplant patients with urinary tract infection by quantitative RT-PCR. The miR-10b and miR-210 were downregulated and miR-10a upregulated in patients with acute rejection compared to controls. Only miR-210 differed between patients with acute rejection when compared to stable transplant patients with urinary tract infection or transplant patients before/after rejection. Low miR-210 levels were associated with higher decline in GFR 1 year after transplantation. Selected miRNAs are strongly altered in urine of the patients with acute renal allograft rejection. The miR-210 levels identify patients with acute rejection and predict long-term kidney function. Urinary miR-210 may thus serve as a novel biomarker of acute kidney rejection.
微小 RNA(miRNAs)是一种调节基因表达的小核糖核苷酸。循环 miRNA 在血液中非常稳定。我们检测了 miRNA 是否也能在尿液中检测到,并可能成为急性肾移植排斥反应患者预后的新预测指标。我们对稳定的移植患者和急性排斥反应的移植患者的尿 miRNA 进行了分析。miR-10a、miR-10b 和 miR-210 在急性排斥反应患者的尿液中明显失调。我们通过定量 RT-PCR 在 62 例急性排斥反应患者、19 例无排斥反应的对照移植患者和 13 例尿路感染的稳定移植患者的尿液中验证了这些数据。与对照组相比,miR-10b 和 miR-210 在急性排斥反应患者中下调,而 miR-10a 上调。与尿路感染的稳定移植患者或排斥反应前后的移植患者相比,miR-210 仅在急性排斥反应患者中存在差异。miR-210 水平较低与移植后 1 年 GFR 下降较高有关。选定的 miRNA 在急性肾移植排斥患者的尿液中发生强烈改变。miR-210 水平可识别急性排斥反应患者,并预测长期肾功能。尿 miR-210 可能因此成为急性肾排斥反应的一种新的生物标志物。