Lewandowska Lidia, Matuszkiewicz-Rowińska Joanna, Jayakumar Calpurnia, Oldakowska-Jedynak Urszula, Looney Stephen, Galas Michalina, Dutkiewicz Małgorzata, Krawczyk Marek, Ramesh Ganesan
Department of Nephrology, Dialysis & Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
Vascular Biology Center, Georgia Regents University, Augusta, GA, United States of America.
PLoS One. 2014 Oct 7;9(10):e107898. doi: 10.1371/journal.pone.0107898. eCollection 2014.
Acute kidney injury (AKI) is a serious complication after liver transplantation. Currently there are no validated biomarkers available for early diagnosis of AKI. The current study was carried out to determine the usefulness of the recently identified biomarkers netrin-1 and semaphorin 3A in predicting AKI in liver transplant patients. A total of 63 patients' samples were collected and analyzed. AKI was detected at 48 hours after liver transplantation using serum creatinine as a marker. In contrast, urine netrin-1 (897.8 ± 112.4 pg/mg creatinine), semaphorin 3A (847.9 ± 93.3 pg/mg creatinine) and NGAL (2172.2 ± 378.1 ng/mg creatinine) levels were increased significantly and peaked at 2 hours after liver transplantation but were no longer significantly elevated at 6 hours after transplantation. The predictive power of netrin-1, as demonstrated by the area under the receiver-operating characteristic curve for diagnosis of AKI at 2, 6, and 24 hours after liver transplantation was 0.66, 0.57 and 0.59, respectively. The area under the curve for diagnosis of AKI was 0.63 and 0.65 for semaphorin 3A and NGAL at 2 hr respectively. Combined analysis of two or more biomarkers for simultaneous occurrence in urine did not improve the AUC for the prediction of AKI whereas the AUC was improved significantly (0.732) only when at least 1 of the 3 biomarkers in urine was positive for predicting AKI. Adjusting for BMI, all three biomarkers at 2 hours remained independent predictors of AKI with an odds ratio of 1.003 (95% confidence interval: 1.000 to 1.006; P = 0.0364). These studies demonstrate that semaphorin 3A and netrin-1 can be useful early diagnostic biomarkers of AKI after liver transplantation.
急性肾损伤（AKI）是肝移植术后的一种严重并发症。目前尚无经过验证的生物标志物可用于AKI的早期诊断。开展本研究以确定最近发现的生物标志物netrin-1和信号素3A在预测肝移植患者AKI方面的效用。共收集并分析了63例患者的样本。以血清肌酐为标志物，在肝移植后48小时检测到AKI。相比之下，尿netrin-1（897.8±112.4 pg/mg肌酐）、信号素3A（847.9±93.3 pg/mg肌酐）和中性粒细胞明胶酶相关脂质运载蛋白（NGAL，2172.2±378.1 ng/mg肌酐）水平显著升高，并在肝移植后2小时达到峰值，但在移植后6小时不再显著升高。netrin-1的预测能力，通过肝移植后2、6和24小时诊断AKI的受试者工作特征曲线下面积分别为0.66、0.57和0.59来证明。信号素3A和NGAL在2小时诊断AKI的曲线下面积分别为0.63和0.65。对尿液中同时出现的两种或更多生物标志物进行联合分析，并未改善预测AKI的曲线下面积（AUC），而只有当尿液中3种生物标志物中至少有1种预测AKI呈阳性时，AUC才显著提高（0.732）。校正体重指数（BMI）后，2小时时所有3种生物标志物仍是AKI的独立预测因子，比值比为1.003（95%置信区间：1.000至1.006；P = 0.0364）。这些研究表明，信号素3A和netrin-1可能是肝移植术后AKI有用的早期诊断生物标志物。
