Division of Nephrology, H040, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
Clin J Am Soc Nephrol. 2010 Mar;5(3):395-401. doi: 10.2215/CJN.05140709. Epub 2009 Dec 10.
Netrin-1, a laminin-related axon guidance molecule, is highly induced and excreted in the urine after acute kidney injury (AKI) in animals. Here, we determined the utility of urinary netrin-1 levels to predict AKI in humans undergoing cardiopulmonary bypass (CPB).
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Serial urine samples were analyzed by enzyme-linked immunosorbent assay for netrin-1 in 26 patients who developed AKI (defined as a 50% or greater increase in serum creatinine after CPB) and 34 controls (patients who did not develop AKI after CPB).
Using serum creatinine, AKI was detected on average only 48 hours after CPB. In contrast, urine netrin-1 increased at 2 hours after CPB, peaked at 6 hours (2462 +/- 370 pg/mg creatinine), and remained elevated up to 48 hours after CPB. The predictive power of netrin-1 as demonstrated by area under the receiver-operating characteristics curve for diagnosis of AKI at 2, 6, and 12 hours after CPB was 0.74, 0.86, and 0.89, respectively. The 6-hour urine netrin-1 measurement strongly correlated with duration and severity of AKI, as well as length of hospital stay (all P < 0.05). Adjusting for CPB time, the 6-hour netrin-1 remained a powerful independent predictor of AKI, with an odds ratio of 1.20 (95% confidence interval: 1.08 to 1.41; P = 0.006).
Our results suggest that netrin-1 is an early, predictive biomarker of AKI after CPB and may allow for the reliable early diagnosis and prognosis of AKI after CPB, before the rise in serum creatinine.
轴突导向分子神经导向因子 1（Netrin-1）在动物急性肾损伤（AKI）后大量诱导并分泌到尿液中。在此，我们旨在确定尿 Netrin-1 水平对接受体外循环（CPB）的患者 AKI 的预测价值。
设计、设置、参与者和测量：通过酶联免疫吸附试验（ELISA）分析 26 例发生 AKI（CPB 后血清肌酐增加 50%或以上定义为 AKI）患者和 34 例对照组（CPB 后未发生 AKI 的患者）的连续尿液样本。
使用血清肌酐，CPB 后平均仅 48 小时检测到 AKI。相比之下，尿 Netrin-1 在 CPB 后 2 小时增加，6 小时达到峰值（2462 +/- 370 pg/mg 肌酐），并在 CPB 后 48 小时内持续升高。在 CPB 后 2、6 和 12 小时，ROC 曲线下面积（AUC）显示 Netrin-1 对 AKI 的诊断预测能力分别为 0.74、0.86 和 0.89。6 小时尿 Netrin-1 测量与 AKI 的持续时间和严重程度以及住院时间长度密切相关（均 P < 0.05）。调整 CPB 时间后，6 小时 Netrin-1 仍然是 AKI 的有力独立预测因子，比值比为 1.20（95%置信区间：1.08 至 1.41；P = 0.006）。
我们的研究结果表明，Netrin-1 是 CPB 后 AKI 的早期预测性生物标志物，可能在血清肌酐升高之前，可靠地早期诊断和预测 CPB 后 AKI。
