Plasma proenkephalin A 119–159 and dipeptidyl peptidase 3 on admission after cardiac arrest help predict long-term neurological outcome

Abstract

Background: A large proportion of adult survivors of cardiac arrest have a poor neurological outcome. Guidelines recommend multimodal neuroprognostication no earlier than 72À96 h after cardiac arrest. There is great interest in earlier prognostic markers, including very early markers at admission. The novel blood biomarkers proenkephalin A 119À159 (penKid), bioactive adrenomedullin (bio-ADM) and circulating dipeptidyl peptidase 3 (cDPP3) have not been previously investigated for the early prognosis of cardiac arrest survivors.Methods: This multicentre observational study included adult survivors of cardiac arrest admitted to intensive care at four Swedish intensive care units (ICUs) during 2016. Blood samples were collected at ICU admission and batch analysed. The association between admission plasma penKid, bio-ADM and cDPP3 and poor long-term neurological outcome, according to the Cerebral Performance Category (CPC) scale, was assessed by binary logistic regression. Their prognostic performance was assessed using the area under the receiver operating characteristic curve (AUC).Results: A total of 190 patients were included, of which 136 patients had suffered out-of-hospital and 54 patients in-hospital cardiac arrest. Poor longterm neurological outcome was associated with elevated admission plasma concentrations of penKid and cDPP3, but not with bio-ADM. The association for penKid, but not for cDPP3, remained after adjusting for clinical cardiac arrest variables with prognostic value (time to return of spontaneous circulation (ROSC), initial rhythm, admission Glasgow coma scale (GCS) motor score and absence of pupillary reflexes). The prognostic performance of above mentioned clinical cardiac arrest variables alone was very good with an AUC of 0.90 (95% confidence interval, CI, 0.86À0.95), but improved further with the addition of penKid resulting in an AUC of 0.93 (95% CI 0.89À0.97, p < 0.026). Plasma penKid and cDPP3 alone provided moderate long-term prognostic information with AUCs of 0.70 and 0.71, respectively. Conclusion:After cardiac arrest, admission plasma levels of penKid and cDPP3, but not bio-ADM, predicted long-term neurological outcome. When added to clinical cardiac arrest variables, penKid further improved prognostic performance.

Dipeptidyl Peptidase 3 Activity as a Promising Biomarker of Bone Fragility in Postmenopausal Women

“…Notably, we revealed here that lower circulating Dpp3 enzymatic levels are associated with a worse skeletal phenotype; conversely, in sepsis, cardiogenic shock, heart failure, and acute kidney injury the correlation goes in the opposite direction, with higher levels resulting in more severe disease and reduced survival rate [19][20][21][22][23][24][25]. In these conditions, angiotensin 2, the primary effector of the renin-angiotensin system (RAS), is recognized as the key substrate of Dpp3 activity and clinical evidence has been interpreted based on the modulation of the RAS by Dpp3, and the resulting impact on hemodynamics and on the physiology of the cardiovascular system.…”

Plasma proenkephalin and neutrophil gelatinase-associated lipocalin predict mortality in ICU patients with acute kidney injury

“…In a study of patients discharged from an ICU ( n = 1,207), higher p-PENK and p-NGAL levels measured at ICU discharge were associated with poor one-year outcomes, including in patients with low serum creatinine levels at ICU discharge [ 17 ]. These two biological indicators are considered to be good predictors of mortality in patients with acute kidney injury in the ICU [ 33 ]. Our study offers new insight into predicting mortality in patients in the ICU with AKI.…”

“…[25] Recent studies have shown that high PENK levels can predict a worsened prognosis in patients with heart failure [21]. Current literature primarily recognizes PENK for its predictive capabilities regarding AKI occurrence [26][27][28][29], and CKD development [30], recovery of kidney function [31], mortality in severe illnesses [17,19,27], extended ICU stays and heightened mortality post-cardiac surgery [32], and recovery from neurological dysfunction [33][34][35]. The novelty of our study lies in demonstrating that plasma PENK not only predicts mortality in ICU patients with AKI but also, when combined with NGAL, significantly enhances mortality prediction in this patient group.…”