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

Abstract

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 GFR-equation (eGFRPENK-Crea), outperforms current creatinine-based eGFR equations in predicting iohexol or iothalamate plasma clearance based measured GFR (mGFR). In this study, we aimed to evaluate the predictive value of penKid and eGFRPENK-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 < 0.0001). Univariable cox regression analyses found penKid and eGFRPENK-Crea to be associated with all-cause mortality (C index: 0.703, χ2: 33.27, P < 0.00001; C index: 0.716, χ2: 36.51, P < 0.00001). 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, χ2: 72.06, P < 0.00001). Importantly, penKid provided significant added value on top of eGFRCKD-EPI 2021 (eGFRCKD-EPI 2021: C index: 0.716, χ2: 34.21; eGFRCKD-EPI 2021 + penKid: C index: 0.727, χ2: 40.02; Delta Chi2: 5.81; all P < 0.00001) for all-cause mortality prediction in our cohort. Conclusions PenKid levels and eGFRPENK-Crea is associated with all-cause mortality within a three-year follow-up period and the addition of penKid on top of eGFRCKD-EPI 2021 provided significant added value in mortality prediction.