Background: Proenkephalin A 119-159 (penKid) is a dynamic blood biomarker for real-time assessment of kidney function. PenKid was recently found to be associated with heart failure development after myocardial infarction and worse cardiorenal function and prognosis in patients with heart failure. The aim of this study was to assess the predictive capacity of penKid levels for outcome in stable patients at high cardiovascular risk. 

 

Methods: Circulating penKid levels were assessed in n=615 patients with high cardiovascular risk (T2D, CAD, CKD and/or CHF) hospitalized at the Department of Cardiology at University Hospital Aachen, Germany. Primary endpoint evaluated was all-cause mortality; follow up was 3 years.

 

Results: Median penKid levels were 35.1 pmol/L for patients with eGFR > 90 mL/min/1.73 m2 (n=128), 42.0 pmol/L for eGFR 60-90 mL/min/1.73 m2 (n=353), 66.3 pmol/L for eGFR 30-60 mL/min/1.73 m2 (n=125) and 113.4 pmol/L for eGFR < 30 mL/min/1.73 m2 (n=9; p<0.0001). PenKid levels were higher in 46 non-survivors (58.8 [IQR 47.5-85.0] pmol/L) compared to 569 survivors (43.8 [IQR 34.0-58.0] pmol/L); p<0.0001). Univariable Cox regression analyses found penKid to be associated with all-cause mortality [standardized hazard ratio (HR) 2.7, 95 % confidence interval (CI): 2.0-3.6; c index 0.70; χ2: 33.3, p<0.0001]. PenKid proved to be superior to the renal injury markers creatinine (AUC: 0.63, χ2: 19.2) and eGFR (AUC: 0.68, χ2: 23.5) and other risk markers including hs-CRP (AUC: 0.69, χ2: 12.4), hs-Troponin T (AUC: 0.62, χ2: 2.0), and HbA1c (AUC: 0.65, χ2: 13.8). Importantly, penKid provided added value on top of creatinine (p<0.0001) and eGFR (p<0.0001). 

 

Conclusion: PenKid is a strong biomarker for all-cause mortality and proved to be superior to other established risk markers in stable patients with high cardiovascular risk.