Predictive Value of Point-of-Care Proenkephalin for Worsening Renal Function and Mortality in Patients Presenting to...

Background: Enkephalins are endogenous opioid peptides that modulate cardiovascular and renal function and are overexpressed in patients with acute heart failure (AHF). Although biologically active enkephalins lack a favorable biomarker profile, their stable surrogate proenkephalin 119-159 (PENK) appears to display prognostic value in AHF settings. The aim of the present study was to evaluate the role of point-of-care (POC) PENK in predicting mortality and worsening renal function (WRF) in patients presenting to the emergency department (ED) with AHF. Methods: In this single-center observational study, 107 patients presenting to the ED with AHF were prospectively enrolled. We measured PENK levels upon ED presentation with a commercially available POC immunoassay and investigated their association with WRF within 48 h and all-cause mortality during a 1-year follow-up. Results: The patients had a mean age of 72 ± 13 years, and 58% were men. Moreover, 62% had acutely decompensated chronic heart failure (HF), 24% had pulmonary edema, 9% had cardiogenic shock, and 5% had right HF. The median PENK levels were 111 [60-193] pmol/L. PENK was independently associated with WRF (adjusted OR, 95% CI: 15.4 [2.0-120.2]; p = 0.009), with levels of ≥90.5 pmol/L identified as the optimal cut-off for predicting WRF (AUC: 0.690; p < 0.001). PENK was also an independent predictor of short- and long-term all-cause mortality, with an optimal cut-off of ≥95.8 pmol/L (AUC for 30-day, 90-day, and 1-year mortality: 0.717, 0.723, and 0.724, respectively; all p < 0.001). Conclusions: In patients presenting to the ED with AHF, POC PENK may serve as an early prognostic marker of WRF and short- and long-term mortality.