Proenkephalin A 119-159 (penKid) – a novel biomarker for acute kidney injury in sepsis: An observational study.

Abstract

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 (6AM-6PM) between December 1, 2013 and February 1, 2015. 56 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 hours 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.

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

“…Association of PENK with AKI has been demonstrated in multiple cohorts of critically ill patients [4, 6, 9, 10, 23-25]. In a study of 956 patients with sepsis, PENK independently predicted the occurrence of AKI within 48 h and 7 days of admission (adjusted OR = 3.3; CI [2.1–5.1] and adjusted OR = 2.1; CI [1.7–2.8], respectively) [6].…”

“…In a subgroup analysis of 299 patients with eGFR > 70 mL/min/1.73 m 2 on admission, PENK levels were still associated with AKI (adjusted OR = 1.9; CI [1.0–3.4], p = 0.04). In another cohort of septic patients ( n = 644), admission plasma PENK levels predicted AKI within 48 h and 7 days [10]. Additionally, PENK levels significantly predicted progression of rSOFA scores from 0 to ≤1 to higher rSOFA scores.…”