Proenkephalin A 119-159 (penKid) and mortality in stable patients at high cardiovascular risk

Background: Proenkephalin A 119-159 (penKid) is a novel blood biomarker for real-time assessment of kidney function and was found to be independently associated with worsening kidney function and mortality. A novel penKid-based estimated glomerular filtration rate equation (eGFR_PENK-Crea), outperforms current creatinine-based eGFR equations in predicting iohexol or iothalamate plasma clearance-based measured GFR. In this study, we aimed to evaluate the predictive value of penKid and eGFR_PENK-Crea for all-cause mortality in stable patients at high cardiovascular risk.

Methods: Circulating penKid levels were assessed in 615 stable patients hospitalized at the Department of Cardiology at University Hospital Aachen, Germany. The endpoint was all-cause mortality; follow up was 3 years.

Results: 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 < .0001]. Univariable Cox regression analyses found penKid and eGFR_PENK-Crea to be associated with all-cause mortality (C index 0.703, χ ² 33.27, P < .00001; C index 0.716, χ ² 36.51, P < .00001). This association remained significant after adjustment for significant baseline parameters including age, smoking, chronic heart failure, use of diuretics, leucocytes, body mass index, sex, and creatinine (C index 0.799, χ ² 72.06, P < .00001). Importantly, penKid provided significant added value on top of eGFR_{CKD-EPI 2021} (eGFR_{CKD-EPI 2021}: C index 0.716, χ ² 34.21; eGFR_{CKD-EPI 2021} + penKid: C index 0.727, χ ²: 40.02; Delta χ ² 5.81; all P < .00001) for all-cause mortality prediction in our cohort.

Conclusions: penKid levels and eGFR_PENK-Crea is associated with all-cause mortality within a 3-year follow-up period and the addition of penKid on top of eGFR_{CKD-EPI 2021} provided significant added value in mortality prediction.