or AKI-RRT even of one of the most extensively evaluated novel urinary biomarkers, neutrophil gelatinase–associated lipocalin (NGAL), appears to be only moderate. We aimed to determine whether the NGAL/hepcidin-25 ratio (urinary concentrations of NGAL divided by that of hepcidin-25) early after surgery may compare favorably to NGAL for identification of high-risk patients after cardiac surgery. METHODS: This is a prospective substudy of the BICARBONATE trial, a multicenter parallel-randomized controlled trial comparing perioperative bicarbonate infusion for AKI prevention to usual patient care. At a tertiary referral center, 198 patients at increased kidney risk undergoing cardiac surgery with cardiopulmonary bypass were included into the present study. The primary outcome measure was defined as AKI-RRT. Secondary outcomes were in-hospital mortality and long-term mortality. We compared area under the curve of the receiver operating characteristic (AUC-ROC) of urinary NGAL with that of the urinary NGAL/hepcidin-25 ratio within 60 minutes after end of surgery. We compared adjusted AUC and performed cross-validated reclassification statistics of the (logarithmic) urinary NGAL/hepcidin-25 ratio adjusted to Cleveland risk score/EuroScore, cross-clamp time, age, volume of packed red blood cells, and (logarithmic) urinary NGAL concentration. The association of the NGAL/hepcidin-25 ratio with long-term patient survival was assessed using Cox proportional hazard regression analysis adjusting for EuroScore, aortic cross-clamp time, packed red blood cells and urinary NGAL. RESULTS: Patients with AKI-RRT (n = 13) had 13.7-times higher NGAL and 3.3-times lower hepcidin-25 concentrations resulting in 46.9-times higher NGAL/hepcidin-25 ratio early after surgery compared to patients without AKI-RRT. The NGAL/hepcidin-25 ratio had higher AUC-ROC compared with NGAL for risk of AKI-RRT and in-hospital mortality (unadjusted AUC-ROC difference 0.087, 95% confidence interval [CI], 0.036–0.138, P < .001; 0.082, 95% CI, 0.018–0.146, P = .012). For AKI-RRT, the NGAL/hepcidin-25 ratio increased adjusted category-free net reclassification improvement (cfNRI; 0.952, 95% CI, 0.437–1.468; P < .001) and integrated discrimination improvement (IDI; 0.040, 95% CI, 0.008–0.073; P = .016) but not AUC difference. For in-hospital mortality, the ratio improved AUC of the reference model (AUC difference 0.056, 95% CI, 0.003–0.108; P = .037) and cfNRI but not IDI. The urinary NGAL/hepcidin-25 ratio remained significantly associated with long-term mortality after adjusting for the model covariates. CONCLUSIONS: The urinary NGAL/hepcidin-25 ratio appears to early identify high-risk patients and outperform NGAL after cardiac surgery. Confirmation of our findings in other cardiac surgery centers is now needed....

中文翻译：

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尿中性粒细胞明胶酶相关的脂质运载蛋白/铁调素 25 比率用于早期识别心脏手术后有肾脏替代治疗风险的患者：碳酸氢盐试验的子研究

或 AKI-RRT 甚至是评估最广泛的新型尿液生物标志物之一，中性粒细胞明胶酶相关脂质运载蛋白 (NGAL)，似乎只是中等。我们旨在确定手术后早期的 NGAL/hepcidin-25 比值（NGAL 的尿液浓度除以 hepcidin-25 的浓度）是否在识别心脏手术后的高危患者方面优于 NGAL。方法：这是 BCARBONATE 试验的前瞻性子研究，这是一项多中心平行随机对照试验，比较围手术期输注碳酸氢盐预防 AKI 与常规患者护理。在三级转诊中心，本研究纳入了 198 名接受体外循环心脏手术的肾脏风险增加的患者。主要结局指标定义为 AKI-RRT。次要结果是住院死亡率和长期死亡率。我们比较了手术结束后 60 分钟内尿 NGAL 的受试者工作特征曲线下面积 (AUC-ROC) 与尿 NGAL/hepcidin-25 比率的曲线下面积。我们比较了调整后的 AUC 并进行了（对数）尿 NGAL/hepcidin-25 比率的交叉验证重新分类统计，调整到克利夫兰风险评分/EuroScore、交叉钳夹时间、年龄、红细胞体积和（对数）尿NGAL 浓度。NGAL/hepcidin-25 比率与长期患者存活率的关联使用 Cox 比例风险回归分析评估，调整 EuroScore、主动脉交叉钳夹时间、浓缩红细胞和尿 NGAL。结果：AKI-RRT 患者（n = 13）的 NGAL 高 13.7 倍，NGAL 高 3 倍。与没有 AKI-RRT 的患者相比，hepcidin-25 浓度降低 3 倍，导致手术后早期 NGAL/hepcidin-25 比值高 46.9 倍。与 NGAL 相比，NGAL/hepcidin-25 比率在 AKI-RRT 风险和院内死亡率方面具有更高的 AUC-ROC（未调整的 AUC-ROC 差异 0.087，95% 置信区间 [CI]，0.036–0.138，P < .001 ; 0.082, 95% CI, 0.018–0.146, P = .012)。对于 AKI-RRT，NGAL/hepcidin-25 比率增加了调整后的无类别净重分类改进（cfNRI；0.952，95% CI，0.437–1.468；P < .001）和综合鉴别改进（IDI；0.040，95% CI , 0.008–0.073; P = .016) 但不是 AUC 差异。对于院内死亡率，该比率改善了参考模型的 AUC（AUC 差异 0.056，95% CI，0.003–0.108；P = .037）和 cfNRI，但不改善 IDI。在调整模型协变量后，尿 NGAL/hepcidin-25 比率仍然与长期死亡率显着相关。结论：尿 NGAL/hepcidin-25 比值似乎可以早期识别高危患者，并优于心脏手术后的 NGAL。现在需要在其他心脏手术中心确认我们的发现......