Plasma proenkephalin A 119–159 on intensive care unit admission is a predictor of organ failure and 30-day mortality

Background Proenkephalin A 119-159 (penKid) has been suggested as a marker of renal failure and poor outcome. We aimed to investigate the association of penKid on ICU admission with organ dysfunction and mortality in a mixed ICU population. In this retrospective, observational study, admission penKid levels from prospectively collected blood samples of consecutive patients admitted to four Swedish ICUs were analysed. The association of penKid with day-two sequential organ failure assessment (SOFA) scores and 30-day mortality was investigated using (ordinal) logistic regression. The predictive power of penKid for 30-day mortality and dialysis was assessed using the area under the receiver operating characteristic curve (AUC). Results Of 1978 included patients, 632 fulfilled the sepsis 3-criteria, 190 had a cardiac arrest, and 157 had experienced trauma. Admission penKid was positively associated with 30-day mortality with an odds ratio of 1.95 (95% confidence interval 1.75–2.18, p < 0.001), and predicted 30-day mortality in the entire ICU population with an AUC of 0.71 (95% confidence interval 0.68–0.73) as well as in the sepsis, cardiac arrest and trauma subgroups (AUCs of 0.61–0.84). Correction for admission plasma creatinine revealed that penKid correlated with neurological dysfunction. Conclusion Plasma penKid on ICU admission is associated with day-two organ dysfunction and predictive of 30-day mortality in a mixed ICU-population, as well as in sepsis, cardiac arrest and trauma subgroups. In addition to being a marker of renal dysfunction, plasma penKid is associated with neurologic dysfunction in the entire ICU population, and cardiovascular dysfunction in sepsis.

Proenkephalin: A New Biomarker for Glomerular Filtration Rate and Acute Kidney Injury

Assessment of kidney function is primarily based on urine output and Creatinine (Cr)-based methods to estimate glomerular filtration rate (GFR). The latter is confounded as Cr is not exclusively filtered by the kidney and rises relatively late after the onset of acute kidney injury (AKI). This leads to delays in recognition of reduced kidney function and diagnosis of AKI, particularly in critically ill patients where kidney function can change rapidly. The gold standard methods of GFR determination, such as inulin or iohexol clearance, are labor intensive and unfeasible in acute clinical settings. Proenkephalin A 119–159 (PENK) has been intensively studied as a novel biomarker of kidney function. PENK belongs to the enkephalin peptide family and is freely filtrated in the glomerulus. Plasma PENK concentration appears to correlate strongly with GFR. Moreover, increased plasma PENK concentrations are found to be associated with long-term kidney outcomes and mortality. In this review, we summarize the role of PENK in assessment of kidney function and its capacity to predict various clinical outcomes.

Proenkephalin A Adds No Incremental Prognostic Value After Acute Ischemic Stroke

Objective: The aim of this study was to confirm previous observations that proenkephalin A (PENK-A) may serve as prognostic marker in the setting of acute ischemic stroke in a large stroke cohort. Methods: The plasma concentration of PENK-A was measured within 72 hours of symptom onset in 320 consecutively enrolled patients with stroke. The primary outcome measures were unfavorable functional outcome (modified Rankin Scale score 0-2 vs 3-6) and mortality within 90 days. Logistic and cox proportional regression analyses were fitted to estimate odds ratios (ORs), hazard ratios (HRs) and 95% confidence intervals (CIs), respectively, for the association between PENK-A and the primary outcome measures. Results: After adjusting for demographic and vascular risk factors, PENK-A was neither independently associated with functional outcome (OR: 1.29, 95% CI: 0.16-10.35) nor mortality (HR: 1.02, 95% CI: 0.14-7.33). Conclusion: Among patients with acute stroke, PENK-A does not serve as an independent prognostic marker in this external validation cohort.

Proenkephalin a 119–159 (penKid) – a novel biomarker for acute kidney injury in sepsis: an observational study

Background Sepsis is a leading cause of death worldwide and a major challenge for physicians to predict and manage. Proenkephalin A 119–159 (penKid) is a reliable surrogate marker for the more unstable endogenous opioid peptide enkephalin, which has previously been shown to predict both acute and chronic kidney disease. The aim of this prospective observational study was to assess penKid as a predictor of acute kidney injury (AKI), multi-organ failure and mortality in sepsis among unselected sepsis patients presenting to the emergency department (ED). Method We enrolled 644 patients consecutively during office-hours (6 AM-6 PM) between December 1, 2013 and February 1, 2015. Fifty-six patients were excluded due to incomplete data. We measured penKid in 588 adult patients (patients under 18 years of age were excluded) with sepsis (≥2SIRS criteria + suspected infection) upon admission to the ED at Skåne University Hospital, Malmö, Sweden. Logistic regression analysis was used to relate levels of penKid at presentation to AKI, multi-organ failure, 28-day mortality and progression of renal SOFA subscore. Odds ratios are presented as the number of standard deviations from the mean of log-transformed penKid. Results In age and sex adjusted models, penKid predicted AKI within 48 h and 7 days, but these associations were attenuated after additional adjustment for estimated creatinine-based glomerular filtration rate (eGFR). In models adjusted for age, sex and eGFR, penKid significantly predicted progression from rSOFA = 0 and ≤ 1 to higher rSOFA scores as well as multi-organ failure and mortality. In contrast, eGFR did not predict 28-day mortality. Conclusion PenKid is an effective predictor of renal injury, severe multi-organ failure and mortality in unselected sepsis patients presenting to the emergency department.