Wenzl Florian A, Wang Peizhi, Arrigo Mattia, Parenica Jiri, Jones Donald J L, Bruno Francesco, Tarnowski Daniel, Hartmann Oliver, Boucek Lubos, Lang Fabian, Obeid Slayman, Schober Andreas, Kraler Simon, Akhmedov Alexander, Kahles Florian, Schober Alexander, Ow Kok Weng, Ministrini Stefano, Camici Giovanni G, Bergmann Andreas, Liberale Luca, Jarkovsky Jiri, Schweiger Victor, Sandhu Jatinderpal K, von Eckardstein Arnold, Templin Christian, Muller Olivier, Ondrus Tomas, Olic Janet-Jacqueline, Roffi Marco, Räber Lorenz, Cao Thong H, Jungbauer Carsten G, Ng Leong L, Mebazaa Alexandre, Lüscher Thomas F
Center for Molecular Cardiology, University of Zurich, Wagistrasse 12, 8952 Schlieren, Switzerland.
National Disease Registration and Analysis Service, NHS, London, UK.
Eur Heart J. 2025 Jan 3;46(1):38-54. doi: 10.1093/eurheartj/ehae602.
Circulating proenkephalin (PENK) is a stable endogenous polypeptide with fast response to glomerular dysfunction and tubular damage. This study examined the predictive value of PENK for renal outcomes and mortality in patients with acute coronary syndrome (ACS).
Proenkephalin was measured in plasma in a prospective multicentre ACS cohort from Switzerland (n = 4787) and in validation cohorts from the UK (n = 1141), Czechia (n = 927), and Germany (n = 220). A biomarker-enhanced risk score (KID-ACS score) for simultaneous prediction of in-hospital acute kidney injury (AKI) and 30-day mortality was derived and externally validated.
On multivariable adjustment for established risk factors, circulating PENK remained associated with in-hospital AKI [per log2 increase: adjusted odds ratio 1.53, 95% confidence interval (CI) 1.13-2.09, P = .007] and 30-day mortality (adjusted hazard ratio 2.73, 95% CI 1.85-4.02, P < .001). The KID-ACS score integrates PENK and showed an area under the receiver operating characteristic curve (AUC) of .72 (95% CI .68-.76) for in-hospital AKI and .91 (95% CI .87-.95) for 30-day mortality in the derivation cohort. Upon external validation, KID-ACS achieved similarly high performance for in-hospital AKI (Zurich: AUC .73, 95% CI .70-.77; Czechia: AUC .75, 95% CI .68-.81; Germany: AUC .71, 95% CI .55-.87) and 30-day mortality (UK: AUC .87, 95% CI .83-.91; Czechia: AUC .91, 95% CI .87-.94; Germany: AUC .96, 95% CI .92-1.00), outperforming the contrast-associated AKI score and the Global Registry of Acute Coronary Events 2.0 score, respectively.
Circulating PENK offers incremental value for predicting in-hospital AKI and mortality in ACS. The simple six-item KID-ACS risk score integrates PENK and provides a novel tool for simultaneous assessment of renal and mortality risk in patients with ACS.
循环前脑啡肽（PENK）是一种稳定的内源性多肽，对肾小球功能障碍和肾小管损伤反应迅速。本研究探讨了PENK对急性冠状动脉综合征（ACS）患者肾脏结局和死亡率的预测价值。
在来自瑞士的前瞻性多中心ACS队列（n = 4787）以及来自英国（n = 1141）、捷克（n = 927）和德国（n = 220）的验证队列中检测血浆中的前脑啡肽。推导并外部验证了一种用于同时预测住院期间急性肾损伤（AKI）和30天死亡率的生物标志物增强风险评分（KID-ACS评分）。
在对既定风险因素进行多变量调整后，循环PENK仍与住院期间的AKI相关[每log2增加：调整后的优势比为1.53，95%置信区间（CI）为1.13 - 2.09，P = 0.007]以及30天死亡率相关（调整后的风险比为2.73，95% CI为1.85 - 4.02，P < 0.001）。KID-ACS评分纳入了PENK，在推导队列中，其预测住院期间AKI的受试者工作特征曲线下面积（AUC）为0.72（95% CI为0.68 - 0.76），预测30天死亡率的AUC为0.91（95% CI为0.87 - 0.95）。在外部验证中，KID-ACS在预测住院期间AKI方面表现出类似的高性能（苏黎世：AUC为0.73，95% CI为0.70 - 0.77；捷克：AUC为0.75，95% CI为0.68 - 0.81；德国：AUC为0.71，95% CI为0.55 - 0.87）以及30天死亡率方面（英国：AUC为0.87，95% CI为0.83 - 0.91；捷克：AUC为0.91，95% CI为0.87 - 0.94；德国：AUC为0.96，95% CI为0.92 - 1.00），分别优于对比相关的AKI评分和全球急性冠状动脉事件注册2.0评分。
循环PENK在预测ACS患者住院期间的AKI和死亡率方面具有额外价值。简单的六项KID-ACS风险评分纳入了PENK，为同时评估ACS患者的肾脏和死亡风险提供了一种新工具。
