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

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.

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.

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.

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.