Supplementary Material for: Biomarker Predictors of Adverse Acute Kidney Injury Outcomes in Critically Ill Patients: The Dublin Acute Biomarker Group Evaluation Study

<b><i>Background:</i></b> The Dublin Acute Biomarker Group Evaluation (DAMAGE) Study is a prospective 2-center observational study investigating the utility of urinary biomarker combinations for the diagnostic and prognostic assessment of acute kidney injury (AKI) in a heterogeneous adult intensive care unit (ICU) population. The objective of this study is to evaluate whether serial urinary biomarker measurements, in combination with a simple clinical model, could improve biomarker performance in the diagnostic prediction of severe AKI and clinical outcomes such as death and need for renal replacement therapy (RRT). <b><i>Methods:</i></b> Urine was collected daily from patients admitted to the ICU, for a total of 7 post-admission days. Urine biomarker concentrations (neutrophil gelatinase-associated lipocalin [NGAL], α-glutathione S-transferase [GST], π-GST, kidney injury molecule-1 [KIM-1], liver-type fatty acid-binding protein [L-FABP], Cystatin C, creatinine, and albumin) were measured. Urine biomarkers were combined with a clinical prediction of AKI model, to determine ability to predict AKI (any stage, within 2 days or 7 days of ICU admission), or a ­30-day composite clinical outcome (RRT – or death). <b><i>Results:</i></b> A total of 257 (38%) patients developed AKI within 7 days of ICU admission. Of those who developed AKI, 106 (41%) patients met stage 3 AKI within 7 days of ICU admission and 208 patients of the entire study cohort (31%) met the composite clinical endpoint of in-hospital mortality or RRT within 30 days of ICU admission. The addition of urinary NGAL/albumin to the clinical model modestly improved the prediction of AKI, in particular severe stage 3 AKI (area under the curve [AUC] of 0.9 from 0.87, <i>p</i> = 0.369) and the prediction of 30-day RRT or death (AUC 0.83 from 0.79, <i>p</i> = 0.139). <b><i>Conclusion:</i></b> A clinical model incorporating severity of illness, patient demographics, and chronic illness with currently available clinical biomarkers of renal function was strongly predictive of development of AKI and associated clinical outcomes in a heterogeneous adult ICU population. The addition of urinary NGAL/albumin to this simple clinical model improved the prediction of severe AKI, need for RRT and death, but not at a statistically or clinically significant level, when compared to the clinical model alone.

<b><i>背景：</i></b> 都柏林生物标志物小组急性评估（Dublin Acute Biomarker Group Evaluation, DAMAGE）研究是一项前瞻性双中心观察性研究，旨在探究尿液生物标志物联合方案在异质性成人重症监护病房（intensive care unit, ICU）人群中急性肾损伤（acute kidney injury, AKI）的诊断与预后评估价值。本研究的目标为评估系列尿液生物标志物检测联合简易临床模型，是否可提升重症AKI的诊断预测效能，以及改善死亡、需肾脏替代治疗（renal replacement therapy, RRT）等临床结局的预测效果。
<b><i>方法：</i></b> 对ICU收治患者每日收集尿液，连续收集至入院后第7天。检测尿液中以下生物标志物的浓度：中性粒细胞明胶酶相关脂质运载蛋白（neutrophil gelatinase-associated lipocalin, NGAL）、α-谷胱甘肽S-转移酶（α-glutathione S-transferase, GST）、π型谷胱甘肽S-转移酶（π-GST）、肾损伤分子1（kidney injury molecule-1, KIM-1）、肝型脂肪酸结合蛋白（liver-type fatty acid-binding protein, L-FABP）、胱抑素C、肌酐及白蛋白。将尿液生物标志物与AKI临床预测模型相结合，以明确其预测AKI（任意分期，于ICU收治后2天或7天内）或30天复合临床结局（需RRT或死亡）的能力。
<b><i>结果：</i></b> 共有257例（38%）患者于ICU收治后7天内发生AKI。在发生AKI的患者中，106例（41%）于ICU收治后7天内进展为3期AKI；整个研究队列中共208例患者（31%）在ICU收治后30天内达到院内死亡或需RRT的复合临床终点。在临床模型中加入尿液NGAL/白蛋白可轻度提升AKI预测效能，尤其是重症3期AKI（曲线下面积（area under the curve, AUC）从0.87提升至0.9，<i>p</i>=0.369）以及30天内需RRT或死亡的预测效能（AUC从0.79提升至0.83，<i>p</i>=0.139）。
<b><i>结论：</i></b> 纳入疾病严重程度、患者人口学特征、慢性病史以及当前可用的肾功能临床生物标志物的临床模型，可在异质性成人ICU人群中有效预测AKI发生及相关临床结局。相较于单纯临床模型，在该简易临床模型中加入尿液NGAL/白蛋白可提升重症AKI、需RRT治疗及死亡的预测效能，但该提升未达到统计学或临床显著性水平。