【罂粟摘要】游离血红蛋白比值作为体外循环心脏术后急性肾损伤新的生物标志物:一项随机对照试验的二级分析

游离血红蛋白比值作为体外循环心脏术后急性肾损伤新的生物标志物:一项随机对照试验的二级分析

贵州医科大学 高鸿教授课题组

翻译:潘志军   编辑:佟睿    审校:曹莹

     背景

体外循环心脏手术(CPB)对其术后急性肾损伤具有高风险。由于当前诊断策略的局限性,我们试图确定游离血红蛋白(fHb)比值(即CPB末的fHb水平除以基线fHb)是否可以预测体外循环心脏手术后的AKI。

方法

这是一项随机对照试验的二级分析,比较了一氧化氮(干预)和氮气(对照)对心脏手术后AKI的影响(NCT01802619)。对照组共包括110名成年患者。首先,我们通过多变量分析确定fHb比值是否与AKI相关。其次,与单独使用尿生物标志物进行预测相比,我们验证了fHb比值是否可以预测AKI,以及纳入fHb比值是否可以在早期提高预测性能。我们在logistic回归中使用了限制性立方样条以进行模型开发。我们确定了预测性能,包括接受者操作特征曲线(AUC)下的面积和校准(校准图和准确性,即正确预测的数量除以预测总数)。如果适用,我们还使用了AUC值检验、似然比检验和净重新分类指数(NRI)来比较竞争模型之间的预测性能(即分别将fHb比值与中性粒细胞明胶酶相关脂质运载蛋白[NGAL]、N-乙酰基-β-d-氨基葡萄糖苷酶[NAG]和肾损伤分子-1 [KIM-1]进行比较,以及将fHb比值与NGAL、NAG和KIM-1相结合来与单独的尿生物标志物进行比较)。

结果

根据fHb中位数比值分层的数据显示,fHb比值> 2.23的受试者表现出更高的AKI发生率(80.0%对49.1%;P=0.001),且更需要肾脏替代治疗(10.9% vs 0%;P=0.036)以及和fHb比值≤2.23的受试者相比有着更高的院内死亡率(10.9% vs 0%;P=0.036)。在调整预先设定的因素后,fHb比值与AKI相关。fHb比值优于尿生物标志物,最高AUC为0.704 (95%置信区间[CI],0.592-0.804),准确度为0.714 (95% CI,0.579-0.804)。与单独使用尿生物标志物的预测相比,纳入fHb比值实现了更好的区分(AUC检验,P=0.012)、校正(似然比检验,P<0.001;准确度,0.740 [95% CI,0.617-0.832] vs 0.632 [95% CI,0.477-0.748])和早期显著的预测增量(NRI,0.638;95% CI,0.269-1.008;P<0.001)。

结论

这项探索性的、假设生成回顾性观察研究的结果表明,CPB结束时的fHb比值可用作AKI的一种新的、广泛适用的生物标志物。与仅基于尿生物标志物的预测相比,使用fHb比值可能有助于AKI的早期检测。

原始文献来源

Jie Hu, Emanuele Rezoagli, Francesco Zadek, et al. Free Hemoglobin Ratio as a Novel Biomarker of Acute Kidney Injury After On-Pump Cardiac Surgery: Secondary Analysis of a Randomized Controlled Trial[J]. (Anesth Analg 2021 06 01;132(6)).

Free Hemoglobin Ratio as a Novel Biomarker of Acute Kidney Injury After On-Pump Cardiac Surgery: Secondary Analysis of a Randomized Controlled Trial

Abstract

Background: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with a high risk of postoperative acute kidney injury (AKI). Due to limitations of current diagnostic strategies, we sought to determine whether free hemoglobin (fHb) ratio (ie, levels of fHb at the end of CPB divided by baseline fHb) could predict AKI after on-pump cardiac surgery.

Methods: This is a secondary analysis of a randomized controlled trial comparing the effect of nitric oxide (intervention) versus nitrogen (control) on AKI after cardiac surgery (NCT01802619). A total of 110 adult patients in the control arm were included. First, we determined whether fHb ratio was associated with AKI via multivariable analysis. Second, we verified whether fHb ratio could predict AKI and incorporation of fHb ratio could improve predictive performance at an early stage, compared with prediction using urinary biomarkers alone. We conducted restricted cubic spline in logistic regression for model development. We determined the predictive performance, including area under the receiver-operating-characteristics curve (AUC) and calibration (calibration plot and accuracy, ie, number of correct predictions divided by total number of predictions). We also used AUC test, likelihood ratio test, and net reclassification index (NRI) to compare the predictive performance between competing models (ie, fHb ratio versus neutrophil gelatinase-associated lipocalin [NGAL], N-acetyl-β-d-glucosaminidase [NAG], and kidney injury molecule-1 [KIM-1], respectively, and incorporation of fHb ratio with NGAL, NAG, and KIM-1 versus urinary biomarkers alone), if applicable.

Results: Data stratified by median fHb ratio showed that subjects with an fHb ratio >2.23 presented higher incidence of AKI (80.0% vs 49.1%; P=0.001), more need of renal replacement therapy (10.9% vs 0%; P=0.036), and higher in-hospital mortality (10.9% vs 0%; P=0.036) than subjects with an fHb ratio≤2.23. fHb ratio was associated with AKI after adjustment for pre-established factors. fHb ratio outperformed urinary biomarkers with the highest AUC of 0.704 (95% confidence interval [CI], 0.592-0.804) and accuracy of 0.714 (95% CI, 0.579-0.804). Incorporation of fHb ratio achieved better discrimination (AUC test, P=0.012), calibration (likelihood ratio test, P<0.001; accuracy, 0.740 [95% CI, 0.617-0.832] vs 0.632 [95% CI, 0.477-0.748]), and significant prediction increment (NRI, 0.638; 95% CI, 0.269-1.008; P<0.001) at an early stage, compared with prediction using urinary biomarkers alone.

Conclusions:Results from this exploratory, hypothesis-generating retrospective, observational study shows that fHb ratio at the end of CPB might be used as a novel, widely applicable biomarker for AKI. The use of fHb ratio might help for an early detection of AKI, compared with prediction based only on urinary biomarkers.

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