用于梗阻性肾病和临床结局的尿液生物标志物组分析
Analysis of a urinary biomarker panel for obstructive nephropathy and clinical outcomes.
作者信息
Xie Yuanyuan, Xue Wei, Shao Xinghua, Che Xiajing, Xu Weijia, Ni Zhaohui, Mou Shan
机构信息
Department of Nephrology, Molecular Cell Lab for Kidney Disease, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
出版信息
PLoS One. 2014 Nov 17;9(11):e112865. doi: 10.1371/journal.pone.0112865. eCollection 2014.
OBJECTIVES
To follow up renal function changes in patients with obstructive nephropathy and to evaluate the predictive value of biomarker panel in renal prognosis.
METHODS
A total of 108 patients with obstructive nephropathy were enrolled in the study; 90 patients completed the follow-up. At multiple time points before and after obstruction resolution, urinary samples were prospectively collected in patients with obstructive nephropathy; the levels of urinary kidney injury molecule-1 (uKIM-1), liver-type fatty acid-binding protein (uL-FABP), and neutrophil gelatinase associated lipocalin (uNGAL) were determined by enzyme-linked immunosorbent assay (ELISA). After 1 year of follow-up, the predictive values of biomarker panel for determining the prognosis of obstructive nephropathy were evaluated.
RESULTS
uKIM-1 (r = 0.823), uL-FABP (r = 0.670), and uNGAL (r = 0.720) levels were positively correlated with the serum creatinine level (all P<0.01). The levels of uKIM-1, uL-FABP, and uNGAL were higher in the renal function deterioration group than in the renal function stable group. Cox regression analysis revealed that the 72-h postoperative uKIM-1 level and the preoperative and 72-h postoperative uL-FABP levels were all risk factors for renal function deterioration (all P<0.01). The area under the curve of Receiver Operating Characteristic(ROC-AUCs) of 72-h postoperative uKIM-1, preoperative uL-FABP, and 72-h postoperative uL-FABP were 0.786, 0.911, and 0.875, respectively. When the combined preoperative uKIM-1, uL-FABP, and uNGAL levels or combined 72-h postoperative uKIM-1, uL-FABP, and uNGAL levels were considered, the accuracy of prediction for renal prognosis was markedly increased, with an ROC-AUC of 0.967 or 0.964, respectively. Kaplan-Meier survival curve analysis demonstrated that a 72-h postoperative uKIM-1>96.69 pg/mg creatinine (Cr), a preoperative uL-FABP>154.62 ng/mg Cr, and a 72-h postoperative uL-FABP>99.86 ng/mg Cr were all positively correlated with poor prognosis (all P<0.01).
CONCLUSION
Biomarker panel may be used as a marker for early screening of patients with obstructive nephropathy and for determining poor prognosis.
目的
随访梗阻性肾病患者的肾功能变化，并评估生物标志物组合对肾脏预后的预测价值。
方法
本研究共纳入108例梗阻性肾病患者；90例患者完成随访。在梗阻解除前后的多个时间点，前瞻性收集梗阻性肾病患者的尿液样本；采用酶联免疫吸附测定（ELISA）法测定尿肾损伤分子-1（uKIM-1）、肝型脂肪酸结合蛋白（uL-FABP）和中性粒细胞明胶酶相关脂质运载蛋白（uNGAL）的水平。随访1年后，评估生物标志物组合对梗阻性肾病预后的预测价值。
结果
uKIM-1（r = 0.823）、uL-FABP（r = 0.670）和uNGAL（r = 0.720）水平与血清肌酐水平呈正相关（均P<0.01）。肾功能恶化组的uKIM-1、uL-FABP和uNGAL水平高于肾功能稳定组。Cox回归分析显示，术后72小时uKIM-1水平以及术前和术后72小时uL-FABP水平均为肾功能恶化的危险因素（均P<0.01）。术后72小时uKIM-1、术前uL-FABP和术后72小时uL-FABP的受试者操作特征曲线下面积（ROC-AUC）分别为0.786、0.911和0.875。当考虑术前uKIM-1、uL-FABP和uNGAL水平联合或术后72小时uKIM-1、uL-FABP和uNGAL水平联合时，肾脏预后预测的准确性显著提高，ROC-AUC分别为0.967或0.964。Kaplan-Meier生存曲线分析表明，术后72小时uKIM-1>96.69 pg/mg肌酐（Cr）、术前uL-FABP>154.62 ng/mg Cr和术后72小时uL-FABP>99.86 ng/mg Cr均与预后不良呈正相关（均P<0.01）。
结论
生物标志物组合可作为梗阻性肾病患者早期筛查和判断预后不良的标志物。
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