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首页> 外文期刊>American Journal of Physiology >Identification of transcripts associated with renal damage due to ureteral obstruction as candidate urinary biomarkers
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Identification of transcripts associated with renal damage due to ureteral obstruction as candidate urinary biomarkers

机译：鉴定与输尿管阻塞引起的转录物相关的转录物作为候选尿生物标志物

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摘要

Renal obstruction is a common cause of renal failure in adults and children and is suspected when hydronephrosis is detected on imaging. Because not all cases of hydronephrosis are associated with renal damage, biomarkers are needed to guide intervention to relieve obstruction. We performed gene expression profiling on the kidneys from adult mice over a detailed time course after obstruction and compared these data with a neonatal model of bilateral high-grade obstruction induced by conditional deletion of the calcineurin β_1 gene. Having identified a set of 143 transcripts modulated in both adult and neonatal obstruction, we tested their expression in a model of short-term obstruction (1 day), where renal damage is transient and reversible, and long-term obstruction (5 days), where significant renal damage is permanent. A significant number of transcripts increased early after obstruction, and later normalized, while 26 transcripts remained elevated 10 and 28 days after relief of 5 days of ureteral obstruction. With the use of qPCR, elevated levels of several of these candidate RNA biomarkers of renal damage were detected in urine from obstructed mice. In addition, several of these candidate RNA biomarkers of damage resulting from obstruction were detectable in catheterized urine samples from children undergoing surgery for ureteropelvic junction obstruction. Measurement of urinary transcripts modulated in response to renal obstruction could serve as biomarkers of renal damage with important clinical applications.
机译：肾脏梗阻是成人和儿童肾功能衰竭的常见原因，并且当检测到在成像时检测到滋肾效落时怀疑。因为并非所有的肾内血症病例与肾损伤有关，因此需要生物标志物来引导干预以缓解障碍。我们在梗阻后的详细时间课程中对成人小鼠进行了基因表达分析，并将这些数据与通过钙素β_1基因的条件缺失引起的双侧高级梗阻的新生儿模型进行了比较。在成人和新生儿阻塞中鉴定了一种调节的143种转录物，我们在短期梗阻（1天）的模型中测试了它们的表达，其中肾脏损伤是短暂的和可逆的，长期梗阻（5天），如果重要的肾损坏是永久性的。梗阻后早期增加了大量的转录物，后来标准化，而26个转录物仍然在输尿管梗阻5天后升高10和28天。通过使用QPCR，在受阻小鼠中尿液检测肾损伤的几个候选RNA生物标志物的升高。此外，这些候选RNA的几种候选RNA生物标志物由受试者尿液接线梗阻接受手术的儿童的导尿尿液样本中可检测到受阻。响应肾梗阻调节的尿记录物的测量可以用作具有重要临床应用的肾损伤的生物标志物。

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