Proenkephalin improves cardio-renal risk prediction in acute coronary syndromes: the KID-ACS score

Florian A Wenzl; Peizhi Wang; Mattia Arrigo; Jiri Parenica; Donald J L Jones; Francesco Bruno; Daniel Tarnowski; Oliver Hartmann; Lubos Boucek; Fabian Lang; Slayman Obeid; Andreas Schober; Simon Kraler; Alexander Akhmedov; Florian Kahles; Alexander Schober; Kok Weng Ow; Stefano Ministrini; Giovanni G Camici; Andreas Bergmann; Luca Liberale; Jiri Jarkovsky; Victor Schweiger; Jatinderpal K Sandhu; Arnold von Eckardstein; Christian Templin; Olivier Muller; Tomas Ondrus; Janet-Jacqueline Olic; Marco Roffi; Lorenz Räber; Thong H Cao; Carsten G Jungbauer; Leong L Ng; Alexandre Mebazaa; Thomas F Lüscher

doi:10.1093/eurheartj/ehae602

Proenkephalin improves cardio-renal risk prediction in acute coronary syndromes: the KID-ACS score

Eur Heart J. 2025 Jan 3;46(1):38-54. doi: 10.1093/eurheartj/ehae602.

Authors

Florian A Wenzl^{1

2

3

4}, Peizhi Wang^{1

5}, Mattia Arrigo⁶, Jiri Parenica⁷, Donald J L Jones^{8

9

10

11}, Francesco Bruno^{12

13}, Daniel Tarnowski¹⁴, Oliver Hartmann¹⁵, Lubos Boucek¹⁶, Fabian Lang¹⁴, Slayman Obeid¹⁷, Andreas Schober¹⁴, Simon Kraler¹, Alexander Akhmedov¹, Florian Kahles¹⁸, Alexander Schober¹⁴, Kok Weng Ow⁸, Stefano Ministrini¹, Giovanni G Camici^{1

19}, Andreas Bergmann¹⁵, Luca Liberale^{20

21}, Jiri Jarkovsky^{22

23}, Victor Schweiger²⁴, Jatinderpal K Sandhu^{8

9

10}, Arnold von Eckardstein²⁵, Christian Templin²⁴, Olivier Muller²⁶, Tomas Ondrus⁷, Janet-Jacqueline Olic¹⁴, Marco Roffi²⁷, Lorenz Räber²⁸, Thong H Cao^{8

9

10}, Carsten G Jungbauer¹⁴, Leong L Ng^{9

10}, Alexandre Mebazaa^{29

30}, Thomas F Lüscher^{1

13

31

32}

Affiliations

¹ Center for Molecular Cardiology, University of Zurich, Wagistrasse 12, 8952 Schlieren, Switzerland.
² National Disease Registration and Analysis Service, NHS, London, UK.
³ Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
⁴ Department of Clinical Sciences, Karolinska Institutet, Stockholm, Sweden.
⁵ Department of Cardiology, National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
⁶ Department of Internal Medicine, Stadtspital Zurich, Zurich, Switzerland.
⁷ Internal and Cardiology Department, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czechia.
⁸ National Institute for Health and Care Research (NIHR) Leicester Biomedical Research Centre (BRC), Leicester, UK.
⁹ Department of Cardiovascular Sciences, Glenfield Hospital, University of Leicester, Leicester, UK.
¹⁰ Leicester van Geest Multi-OMICS Facility, University of Leicester, Leicester, UK.
¹¹ Leicester Cancer Research Centre and Department of Genetics and Genome Biology, RKCSB, University of Leicester, Leicester, UK.
¹² Division of Cardiology, Cardiovascular and Thoracic Department, Molinette Hospital, Città della Salute e della Scienza, Turin, Italy.
¹³ Royal Brompton and Harefield Hospitals, Sydney Street, London SW3 6NP, UK.
¹⁴ Department of Internal Medicine II (Cardiology), University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
¹⁵ 4teen4 Pharmaceuticals, 16761 Hennigsdorf, Germany.
¹⁶ Department of Laboratory Medicine, Division of Clinical Biochemistry, University Hospital Brno, Brno, Czechia.
¹⁷ Division of Cardiology, Department of Medicine, Basel Cantonal Hospital, Basel, Switzerland.
¹⁸ Department of Internal Medicine I, University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany.
¹⁹ Department of Research and Education, University Hospital Zurich, Zurich, Switzerland.
²⁰ First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy.
²¹ IRCCS Ospedale Policlinico San Martino Genoa-Italian Cardiovascular Network, L.go R. Benzi 10, 16132 Genoa, Italy.
²² Institute of Health Information and Statistics of the Czech Republic, Prague, Czechia.
²³ Faculty of Medicine, Institute of Biostatistics and Analysis, Masaryk University, Brno, Czechia.
²⁴ Department of Cardiology, University Hospital Zurich, Zurich, Switzerland.
²⁵ Institute of Clinical Chemistry, University Hospital Zurich and University of Zuich, Zurich, Switzerland.
²⁶ Service of Cardiology, Lausanne University Hospital, Lausanne, Switzerland.
²⁷ Department of Cardiology, Geneva University Hospital, Geneva, Switzerland.
²⁸ Department of Cardiology, Cardiovascular Center, University Hospital Bern, Bern, Switzerland.
²⁹ Université Paris Cité, INSERM UMR-S 942(MASCOT), Paris, France.
³⁰ Department of Anesthesiology and Critical Care and Burn Unit, Saint-Louis and Lariboisière Hospitals, FHU PROMICE, DMU Parabol, APHP.Nord, Paris, France.
³¹ National Heart and Lung Institute, Imperial College, London, UK.
³² School of Cardiovascular Medicine and Sciences, Kings College London, London, UK.

Abstract

Background and aims: 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).

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Acute coronary syndromes; Acute kidney injury; Mortality risk; Proenkephalin; Risk prediction.

Publication types

Multicenter Study

MeSH terms

Acute Coronary Syndrome* / blood
Acute Coronary Syndrome* / mortality
Acute Kidney Injury*
Aged
Biomarkers* / blood
Enkephalins* / blood
Female
Humans
Male
Middle Aged
Predictive Value of Tests
Prospective Studies
Protein Precursors* / blood
Risk Assessment / methods
Risk Factors

Substances

proenkephalin
Enkephalins
Protein Precursors
Biomarkers

Abstract

Publication types

MeSH terms

Substances

Grants and funding