Zappitelli Michael, Washburn Kimberly K, Arikan Ayse A, Loftis Laura, Ma Qing, Devarajan Prasad, Parikh Chirag R, Goldstein Stuart L
Texas Children's Hospital, Fannin Street, Houston, Texas 77030, USA.
Crit Care. 2007;11(4):R84. doi: 10.1186/cc6089.
Serum creatinine is a late marker of acute kidney injury (AKI). Urine neutrophil gelatinase-associated lipocalin (uNGAL) is an early marker of AKI, where the timing of kidney injury is known. It is unknown whether uNGAL predicts AKI in the general critical care setting. We assessed the ability of uNGAL to predict AKI development and severity in critically ill children.
This was a prospective cohort study of critically ill children. Children aged between 1 month and 21 years who were mechanically ventilated and had a bladder catheter inserted were eligible. Patients with end-stage renal disease or who had just undergone kidney transplantation were excluded. Patients were enrolled within 24 to 48 hours of initiation of mechanical ventilation. Clinical data and serum creatinine were collected daily for up to 14 days from enrollment, and urine was collected once daily for up to 4 days for uNGAL measurement. AKI was graded using pRIFLE (pediatric modified Risk, Injury, Failure, Loss, End Stage Kidney Disease) criteria. Day 0 was defined as the day on which the AKI initially occurred, and pRIFLEmax was defined as the worst pRIFLE AKI grade recorded during the study period. The chi2 test was used to compare associations between categorical variables. Mann-Whitney and Kruskal-Wallis tests were used to compare continuous variables between groups. Diagnostic characteristics were evaluated by calculating sensitivity and specificity, and constructing receiver operating characteristic curves.
A total of 140 patients (54% boys, mean +/- standard deviation Pediatric Risk of Mortality II score 15.0 +/- 8.0, 23% sepsis) were included. Mean and peak uNGAL concentrations increased with worsening pRIFLEmax status (P < 0.05). uNGAL concentrations rose (at least sixfold higher than in controls) in AKI, 2 days before and after a 50% or greater rise in serum creatinine, without change in control uNGAL. The parameter uNGAL was a good diagnostic marker for AKI development (area under the receiver operating characteristic curve [AUC] 0.78, 95% confidence interval [CI] 0.62 to 0.95) and persistent AKI for 48 hours or longer (AUC 0.79, 95% CI 0.61 to 0.98), but not for AKI severity, when it was recorded after a rise in serum creatinine had occurred (AUC 0.63, 95% CI 0.44 to 0.82).
We found uNGAL to be a useful early AKI marker that predicted development of severe AKI in a heterogeneous group of patients with unknown timing of kidney injury.
血清肌酐是急性肾损伤（AKI）的晚期标志物。尿中性粒细胞明胶酶相关脂质运载蛋白（uNGAL）是已知肾损伤发生时间的AKI早期标志物。在一般重症监护环境中，uNGAL是否能预测AKI尚不清楚。我们评估了uNGAL预测危重症儿童AKI发生及严重程度的能力。
这是一项针对危重症儿童的前瞻性队列研究。年龄在1个月至21岁之间、接受机械通气并插入膀胱导管的儿童符合条件。终末期肾病患者或刚接受肾移植的患者被排除。患者在机械通气开始后的24至48小时内入组。从入组起最多14天每天收集临床数据和血清肌酐，最多4天每天收集尿液用于检测uNGAL。使用pRIFLE（儿科改良的风险、损伤、衰竭、失功、终末期肾病）标准对AKI进行分级。第0天定义为AKI最初发生的日子，pRIFLEmax定义为研究期间记录的最严重pRIFLE AKI分级。采用卡方检验比较分类变量之间的关联。使用Mann-Whitney检验和Kruskal-Wallis检验比较组间连续变量。通过计算敏感性和特异性并构建受试者工作特征曲线来评估诊断特征。
共纳入140例患者（54%为男孩，平均±标准差儿科死亡风险II评分为15.0±8.0，23%为脓毒症）。uNGAL的平均浓度和峰值浓度随pRIFLEmax状态恶化而升高（P<0.05）。在AKI患者中，血清肌酐升高50%或更高之前2天和之后2天，uNGAL浓度升高（至少比对照组高6倍），而对照组uNGAL无变化。uNGAL参数是AKI发生（受试者工作特征曲线下面积[AUC]0.78，95%置信区间[CI]0.62至0.95）和持续AKI达48小时或更长时间（AUC 0.79，95%CI 0.61至0.98）的良好诊断标志物，但在血清肌酐升高后记录时，对AKI严重程度不是良好诊断标志物（AUC 0.63，95%CI 0.44至0.82）。
我们发现uNGAL是一种有用的AKI早期标志物，可预测肾损伤发生时间不明的异质性患者群体中严重AKI的发生。
