Urinary Matrix Metalloproteinase-7 Predicts Severe AKI and Poor Outcomes after Cardiac Surgery
Urinary Matrix Metalloproteinase-7 Predicts Severe AKI and Poor Outcomes after Cardiac Surgery
复制标题
尿基质金属蛋白酶 7 可预测严重 AKI 和心脏手术后的不良预后
DOI：
10.1681/asn.2017020142
复制
发表时间：
2017-11-01
影响因子：
13.6
通讯作者：
Hou, Fan Fan
中科院分区：
文献类型：
--
作者：
Yang, Xiaobing;Chen, Chunbo;Hou, Fan Fan
尿基质金属蛋白酶-7（uMMP-7）水平一致地反映了肾内Wnt/β-连环蛋白的活性，其在阿基模型中被激活。为了检验uMMP-7是心脏手术后患者严重阿基的预测因子这一假设，我们在721例接受心脏手术的患者中进行了一项前瞻性、多中心、两阶段队列研究。在第一阶段，我们从三个学术医疗中心招募了323名儿童。在第二阶段，我们在六个中心招募了398名成年人。我们分析了围手术期uMMP-7和其他损伤生物标志物的水平。重度阿基定义为改善全球结局的肾脏疾病2期或3期。uMMP-7水平在术后6小时内达到峰值，随后发生重度阿基。多变量校正后，术后uMMP-7水平最高的五分位数与最低的五分位数相比，与严重阿基的几率高17倍（成人）和36倍（儿童）相关。uMMP-7水平升高与复合事件（重度阿基、急性透析和院内死亡）风险增加以及重症监护室和住院时间延长相关。对于预测重度阿基，uMMP-7的受试者工作特征曲线下面积为0.81（儿童）和0.76（成人），优于尿IL-18、血管紧张素原、中性粒细胞明胶酶相关脂质运载蛋白、白蛋白/肌酐比值、金属蛋白酶组织抑制剂-2、IGF-结合蛋白-7和临床模型。uMMP-7显著改善了单独的临床模型的风险重新分类，如通过净重新分类改善和综合辨别改善所测量的。总之，uMMP-7是心脏手术后患者严重阿基和住院预后不良的有希望的预测因子。
Urinary matrix metalloproteinase-7 (uMMP-7) levels consistently reflect the activity of intrarenal Wnt/beta-catenin, which is activated in AKI models. To test the hypothesis that uMMP-7 is a predictor for severe AKI in patients after cardiac surgery, we performed a prospective, multicenter, two-stage cohort study in 721 patients undergoing cardiac surgery. In stage 1, we enrolled 323 children from three academic medical centers. In stage 2, we enrolled 398 adults at six centers. We analyzed levels of uMMP-7 and other injury biomarkers during the perioperative period. Severe AKI was defined as Kidney Disease Improving Global Outcomes stage 2 or 3. uMMP-7 level peaked within 6 hours after surgery in patients who subsequently developed severe AKI. After multivariate adjustment, the highest quintile of postoperative uMMP-7 level, compared with the lowest quintile, associated with 17-fold (in adults) and 36-fold (in children) higher odds of severe AKI. Elevated uMMP-7 level associated with increased risk of composite events (severe AKI, acute dialysis, and in-hospital death) and longer stay in the intensive care unit and hospital. For predicting severe AKI, uMMP-7 had an area under the receiver operating characteristic curve of 0.81 (in children) and 0.76 (in adults), outperforming urinary IL-18, angiotensinogen, neutrophil gelatinase-associated lipocalin, albumin-to-creatinine ratio, and tissue inhibitor of metalloproteinase-2.IGF-binding protein-7 and the clinical model. uMMP-7 significantly improved risk reclassification over the clinical model alone, as measured by net reclassification improvement and integrated discrimination improvement. In conclusion, uMMP-7 is a promising predictor for severe AKI and poor in-hospital outcomes in patients after cardiac surgery.