Abstract
BackgroundSepsis 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).MethodWe 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.ResultsIn 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.ConclusionPenKid is an effective predictor of renal injury, severe multi-organ failure and mortality in unselected sepsis patients presenting to the emergency department.
Highlights
Sepsis is a leading cause of death worldwide and a major challenge for physicians to predict and manage
PenKid is an effective predictor of renal injury, severe multi-organ failure and mortality in unselected sepsis patients presenting to the emergency department
Characteristics of study subjects A total of 647 patients with sepsis, i.e. fulfilment of two Systemic Inflammatory Response Syndrome (SIRS) criteria and clinical suspicion of infection, were prospectively enrolled after presentation to the emergency department (ED), of whom 588 had complete covariate data used in this study
Summary
Characteristics of study subjects A total of 647 patients with sepsis, i.e. fulfilment of two SIRS criteria and clinical suspicion of infection, were prospectively enrolled after presentation to the ED, of whom 588 had complete covariate data used in this study. Logistic regression adjusted for sex and age yielded an OR for AKI development per z-score of log-transformed penKid of 2.5 (1.9–3.3, p < 0.001) and 2.5 (1.9–3.2, p < 0.001) for 48 h and seven days, respectively. After additional adjustment for baseline eGFR, prediction for rSOFA deterioration remained statistically significant for patients presenting with penKid > 100 pmol/ L vs ≤ 100 pmol/L [OR 3.2, 95% CI 1.1–9.1, p = 0.033]. We tested if penKid > 100 pmol/L vs ≤ 100 pmol/L predicted rSOFA deterioration in all patients with rSOFA = 0 (n = 413) or rSOFA≤1 (n = 526) (i.e. irrespective of limitation of care) using a logistic regression model adjusted for sex, age and eGFR. For a summary of the relationship between other collected variables and MOF and 28-day all-cause mortality, please see Additional file 1: Table S3
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