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中性粒细胞明胶酶相关脂质运载蛋白作为术前存在肾脏损害的心脏手术患者术后急性肾损伤的标志物

Neutrophil Gelatinase-associated Lipocalin as a Marker of Postoperative Acute Kidney Injury Following Cardiac Surgery in Patients with Preoperative Kidney Impairment.

作者信息

Tidbury N, Browning N, Shaw M, Morgan M, Kemp I, Matata B

机构信息

Liverpool Heart & Chest Hospital NHS Foundation Trust, University of Liverpool, Liverpool L14 3PE, United Kingdom.

Department of Clinical Infection, Microbiology and Immunology, University of Liverpool, Liverpool L14 3PE, United Kingdom.

出版信息

Cardiovasc Hematol Disord Drug Targets. 2019;19(3):239-248. doi: 10.2174/1871529X19666190415115106.

Abstract

INTRODUCTION

Acute kidney injury (AKI) is a serious complication of cardiac surgery. The current 'gold standard' for determining AKI is change in serum creatinine and urine output, however, this change occurs relatively late after the actual injury occurs. Identification of new biomarkers that detect early AKI is required. Recently, new biomarkers, such as the NephroCheck® Test and AKIRisk have also been tested and found to be good indicators of AKI. Neutrophil gelatinase-associated lipocalin (NGAL) has shown promise in paediatric patients but has displayed varied results in adult populations, particularly post cardiac surgery. The aim of this study was to assess the value of urinary NGAL as a biomarker of AKI in patients with pre-existing renal impairment (eGFR >15ml/min to eGFR<60ml/min).

METHODS

A post-hoc analysis of urinary NGAL concentrations from 125 patients with pre-existing kidney impairment, who participated in a randomised trial of haemofiltration during cardiac surgery, was undertaken. Urinary NGAL was measured using ELISA at baseline, post-operatively and 24 and 48 hours after surgery, and serum creatinine was measured pre and postoperatively and then at 24, 48, 72 and 96 hours as routine patient care. NGAL concentrations were compared in patients with and without AKI determined by changes in serum creatinine concentrations. A Kaplan-Meier plot compared survival for patients with or without AKI and a Cox proportional hazards analysis was performed to identify factors with the greatest influence on survival.

RESULTS

Following surgery, 43% of patients developed AKI (based on KDIGO definition). Baseline urinary NGAL was not found to be significantly different between patients that did and did not develop AKI. Urinary NGAL concentration was increased in all patients following surgery, regardless of whether they developed AKI and was also significant between groups at 24 (p=0.003) and 48 hours (p<0.0001). Urinary NGAL concentrations at 48 hours correlated with serum creatinine concentrations at 48 hours (r=0.477, p<0.0001), 72 hours (r=0.488, p<0.0001) and 96 hours (r=0.463, p<0.0001). Urinary NGAL at 48 hours after surgery strongly predicted AKI (AUC=0.76; P=0.0001). A Kaplan- Meier plot showed that patients with postoperative AKI had a significantly lower 7-year survival compared with those without AKI. Postoperative urinary NGAL at 48 hours >156ng/mL also strongly predicted 7-year survival. However, additive EuroSCORE, age, current smoking and post-operative antibiotics usage were distinctly significantly more predictive of 7-year survival as compared with postoperative urinary NGAL at 48 hours >156ng/mL.

CONCLUSIONS

Our study demonstrated that postoperative urinary NGAL levels at 48 hours postsurgery strongly predicts the onset or severity of postoperative AKI based on KDIGO classification in patients with preoperative kidney impairment and were also strongly related to 7-year survival.

摘要

引言

急性肾损伤(AKI)是心脏手术的一种严重并发症。目前用于确定AKI的“金标准”是血清肌酐和尿量的变化,然而,这种变化在实际损伤发生后相对较晚才出现。因此需要识别能够检测早期AKI的新生物标志物。最近,诸如NephroCheck®检测和AKIRisk等新生物标志物也经过了测试,并被发现是AKI的良好指标。中性粒细胞明胶酶相关脂质运载蛋白(NGAL)在儿科患者中显示出应用前景,但在成年人群中,尤其是心脏手术后,其结果存在差异。本研究的目的是评估尿NGAL作为已有肾功能损害(估算肾小球滤过率[eGFR]>15ml/min至eGFR<60ml/min)患者AKI生物标志物的价值。

方法

对125例已有肾脏损害且参与心脏手术期间血液滤过随机试验的患者的尿NGAL浓度进行事后分析。在基线、术后以及术后24小时和48小时使用酶联免疫吸附测定(ELISA)法测量尿NGAL,并且在术前和术后以及之后的24、48、72和96小时测量血清肌酐,作为常规患者护理。根据血清肌酐浓度变化确定有无AKI的患者,比较其NGAL浓度。绘制Kaplan-Meier曲线比较有或无AKI患者的生存率,并进行Cox比例风险分析以确定对生存影响最大的因素。

结果

术后,43%的患者发生AKI(基于改善全球肾脏病预后组织[KDIGO]的定义)。未发生和发生AKI的患者之间,基线尿NGAL未发现有显著差异。所有患者术后尿NGAL浓度均升高,无论其是否发生AKI,并且在24小时(p=0.003)和48小时(p<0.0001)组间也有显著差异。48小时的尿NGAL浓度与48小时(r=0.477,p<0.0001)、72小时(r=0.488,p<0.0001)和96小时(r=0.463,p<0.0001)的血清肌酐浓度相关。术后48小时的尿NGAL能有力地预测AKI(曲线下面积[AUC]=0.76;P=0.0001)。Kaplan-Meier曲线显示,术后发生AKI的患者7年生存率显著低于未发生AKI的患者。术后48小时尿NGAL>156ng/mL也能有力地预测7年生存率。然而,与术后48小时尿NGAL>156ng/mL相比,欧洲心脏手术风险评估系统(EuroSCORE)、年龄、当前吸烟状况和术后抗生素使用情况对7年生存率的预测明显更具显著性。

结论

我们的研究表明,术后48小时的尿NGAL水平能有力地预测术前有肾功能损害患者基于KDIGO分类的术后AKI的发生或严重程度,并且也与7年生存率密切相关。

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