Pharmacology Area, Faculty of Biochemistry and Pharmaceutical Sciences, National University of Rosario, CONICET, Rosario, Argentina.
Clin Exp Pharmacol Physiol. 2020 Oct;47(10):1674-1681. doi: 10.1111/1440-1681.13360. Epub 2020 Jun 23.
Ureteral obstruction is a relevant cause of kidney damage. The traditional parameters used in clinical practice for the detection of renal injury are insensitive and non-specific for the diagnosis of obstructive renal disease. The organic anion transporter 5 (Oat5) is a carrier expressed exclusively in the kidney. In this study, the Oat5 urinary excretion (Oat5 ) was evaluated as a potential biomarker of obstructive nephropathy, comparing it with traditional markers of renal function and with neutrophil gelatinase-associated lipocalin in urine (NGAL ), a more recent biomarker of renal pathology. Bilateral ureteral obstruction (BUO) was induced in male Wistar rats, by complete ligation of ureters for 1 hour (BUO1), 2 hours (BUO2), 5 hours (BUO5), or 24 hours (BUO24). After 24 hours of ureteral releasing, urea and creatinine plasma concentrations, creatinine clearance, urinary total proteins, urinary glucose, and alkaline phosphatase activities in urine were evaluated. Oat5 and NGAL levels were assessed in urine samples by immunoblotting. All parameters of renal function were altered in the BUO24 and some also in BUO5, while the Oat5 increased in all of the experimental groups analyzed. After a long time of ureteral obstruction (BUO24), the urinary excretion of Oat5 markedly increased, in parallel with the alteration in the other parameters evaluated. Nevertheless, in BUO1 and BUO2, Oat5 appeared as the only parameter modified. Therefore, Oat5 could be proposed as a novel early biomarker of ureteral obstruction, with the additional potential to inform about the severity of the obstructive injury suffered by the kidney.
输尿管梗阻是肾脏损伤的一个相关原因。在临床实践中用于检测肾损伤的传统参数对梗阻性肾病的诊断不敏感且特异性差。有机阴离子转运体 5（Oat5）是一种仅在肾脏中表达的载体。在这项研究中，将 Oat5 的尿排泄（Oat5）评估为梗阻性肾病的潜在生物标志物，将其与肾功能的传统标志物进行比较，并与尿液中中性粒细胞明胶酶相关脂质运载蛋白（NGAL）进行比较，后者是一种更近期的肾脏病理生物标志物。通过完全结扎输尿管 1 小时（BUO1）、2 小时（BUO2）、5 小时（BUO5）或 24 小时（BUO24），在雄性 Wistar 大鼠中诱导双侧输尿管梗阻（BUO）。在输尿管释放 24 小时后，评估血浆尿素和肌酐浓度、肌酐清除率、尿总蛋白、尿葡萄糖和尿碱性磷酸酶活性。通过免疫印迹法评估尿样中的 Oat5 和 NGAL 水平。在 BUO24 中，所有肾功能参数均发生改变，在 BUO5 中有些参数也发生改变，而 Oat5 在所有分析的实验组中均增加。在输尿管梗阻时间较长（BUO24）后，Oat5 的尿排泄量明显增加，与评估的其他参数的变化平行。然而，在 BUO1 和 BUO2 中，Oat5 似乎是唯一改变的参数。因此，Oat5 可以作为输尿管梗阻的新型早期生物标志物提出，此外还可以提供有关肾脏梗阻性损伤严重程度的信息。
