先天性心脏病患儿术后发生急性肾损伤的危险因素 及早期检测血清microRNA-203 的意义

Risk factors for acute kidney injury after cardiopulmonary bypass and the significance of microRNA-203 in children with congenital heart disease

摘要:

目的 探讨先天性心脏病（以下简称先心病）患儿体外循环术后发生急性肾损伤（AKI）的危险因素， 以及血清microRNA-203（miR-203） 对AKI 的早期临床价值。方法 选取2016 年9 月—2018 年1 月 在华中科技大学同济医学院附属同济医院住院的178 例先心病患儿，根据AKI 诊断标准将患儿分为AKI 组53 例和非AKI 组125 例。观察AKI 发生率，比较两组患儿的临床特征。采用多因素Logistic 回归分析 AKI 的危险因素，qRT-PCR 检测两组患儿术前，以及术后2、12、24 和48 h 的miR-203、肾损伤分子-1 （KIM-1）水平表达量。采用受试者工作特征（ROC）曲线确定术后2 h 血清miR-203 对AKI 的预测价 值，计算曲线下面积（AUC）。结果 术后48 h 内，53 例（29.78%）患儿发生AKI，125 例（70.22%）患儿 未发生AKI。AKI 组患儿年龄小于非AKI 组（P <0.05），术前紫绀型先心病比例、体外循环时间、阻断升主 动脉时间及采用间断性灌注4 ∶ 1 含血高钾停跳液（以下简称血灌）进行心肌保护的比例高于非AKI 组患 儿（P <0.05）。术后AKI 组患儿循环血中KIM-1 和miR-203 水平呈升高趋势（P <0.05），且术后12 h 血清 miR-203 水平达峰值，早于KIM-1 水平达峰时间。ROC 曲线分析，术后2 h 血清miR-203 截断值为1.700， 其预测AKI 发生的AUC 为0.851（95% CI ：0.775，0.928），敏感性为85.42%（95% CI ：0.825，0.874），特异 性为54.17%（95% CI ：0.537，0.587）。经二分类变量Logistic 回归分析，年龄<4 岁[Ol ^ R=1.823（95% CI ： 1.594，3.953），P =0.000]、紫绀型先心病[Ol ^ R=1.461（95% CI ：1.254，1.726），P =0.005]、体外循环时间> 175.68 min [Ol ^ R=2.105（95% CI ：1.587，5.265），P =0.000]、阻断升主动脉时间>101.45 min [Ol ^ R=1.217 （95% CI ：1.082，1.339），P =0.000] 及术后2 h 血清miR-203>1.70。[Ol ^ R=1.331（95% CI ：1.160 ，3.241）， P =0.022] 是发生AKI 的独立危险因素；血灌心肌保护[Ol ^ R=0.729（95% CI ：0.558，0.894），P =0.004] 是发生 AKI 的独立保护因素。结论 先心病纠正术后AKI 的发生与患儿年龄、术前紫绀、体外循环时间、阻断升主 动脉时间、血灌及术后2 h 血清miR-203 有关，且术后miR-203 水平可作为AKI 发生的早期预测因子。

Abstract:

Objective To analyze the risk factors of acute kidney injury (AKI) after extracorporeal circulation (CPB) and the significance of miRNA-203 (miR-203) in early warning of AKI in children with congenital heart disease. Methods A total of 178 children with congenital heart disease ( ≤ 6 years old) who underwent congenital heart surgery in our hospital from September 2016 to January 2018 were enrolled in this research. According to AKI diagnostic criteria, children were divided into AKI group (53 cases) and non AKI group (125 cases). The incidence of AKI was observed. Serum miR-203 expressions were determined by RT-PCR in blood samples before extracorporeal circulation, 2 h, 12 h, 24 h and 48h after extracorporeal circulation. The clinical characteristics of children with and without AKI were compared, and multivariate Logistic regression analysis were used to find out the risk factors of AKI. The receiver operating characteristic (ROC) curve of miR-203 was used to analyze the predictive value for AKI. Results There were 53 children (29.78%) with AKI and 125 patients (70.22%) without AKI. The children in AKI group had lower ages, higher incidence of cyanotic disease, longer extracorporeal circulation duration and occlusion of aorta time, a significantly higher proportion of children receiving crystalloid solution for myocardial protection than those of children without AKI (P < 0.05). In the AKI group, the post-operative kidney injury molecule 1 (KIM-1) and miR-203 increased, while the peak value of KIM-1 achieved at 24 h after surgery and the peak value of miR-203 achieved at 12 h after surgery. When the cut-off was 1.700, the AUC of ROC curve of miR-203 at 2 h after extracorporeal circulation were 0.851 (95% CI: 0.775, 0.928), the sensitivity and specificity were respectively 85.42% (95% CI: 0.825, 0.874) and 54.17% (95% CI: 0.537, 0.587). The age < 4 y [Ol^R=1.823 (95% CI: 1.594, 3.953), P = 0.000], cyanotic disease [Ol^R=1.461 (95% CI: 1.254, 1.726), P = 0.005], extracorporeal circulation duration > 175.68 min [Ol^R=2.105 (95% CI: 1.587, 5.265), P = 0.000], occlusion of aorta time > 101.45 min [Ol^R=1.217 (95% CI: 1.082, 1.339), P = 0.000] and miR-203 at 2h after extracorporeal circulation > 1.70 [Ol^R=1.331 (95% CI: 1.160, 3.241), P = 0.022] were independent risk factors of AKI in children with congenital heart disease (P < 0.05). Conclusion Age, preoperative cyanotic disease, extracorporeal circulation duration, occlusion of aorta time and miR-203 at 2h after extracorporeal circulation are independent factors of AKI after extracorporeal circulation. It’s suggested that miR-203 may be the sensitive predictors of acute kidney injury in children with congenital heart disease.