title: Diagnostic and short-term prognostic utility of plasma pro-enkephalin (pro-ENK) for acute kidney injury in patients admitted with sepsis in the emergency department.
abstract: BACKGROUND
  Acute kidney injury (AKI) aggravates the prognosis of patients with sepsis. Reliable biomarkers for early detection of AKI in this setting are lacking. Enkephalins influence kidney function, and may have a role in AKI from sepsis. We utilized a novel immunoassay for plasma proenkephalin (pro-ENK), a stable surrogate marker for endogenous enkephalins, in patients hospitalized with sepsis, in order to assess its clinical utility.
  
  
  METHODS
  In an observational retrospective study we enrolled 101 consecutive patients admitted to the emergency department (ED) with suspected sepsis. Plasma levels of pro-ENK and neutrophil gelatinase-associated lipocalin (NGAL) were evaluated at ED arrival for their association with presence and severity of AKI and 7-day mortality.
  
  
  RESULTS
  pro-ENK was inversely correlated to creatinine clearance (r = -0.72) and increased with severity of AKI as determined by RIFLE (risk, injury, failure, loss of function, end-stage renal disease) stages (p < 0.0001; pro-ENK median [interquartile range, IQR]) pmol/l: no AKI: 71 [41-97]; risk: 72 [51-120]; injury: 200 [104-259]; failure: 230 [104-670]; loss of function: 947 [273-811]. The majority of septic patients without AKI or at risk had pro-ENK concentrations within the normal range. While NGAL was similarly associated with AKI severity, it was strongly elevated already in septic patients without AKI. pro-ENK added predictive information to NGAL for detecting kidney dysfunction (added χ (2) 10.0, p = 0.0016). Admission pro-ENK outperformed creatinine clearance in predicting 7-day mortality (pro-ENK: χ (2) 13.4, p < 0.001, area under curve, AUC 0.69; creatinine clearance: χ (2) 4, p = 0.045, AUC: 0.61), and serial measurement improved prediction.
  
  
  CONCLUSIONS
  Use of pro-ENK in septic patients can detect the presence and severity of AKI. Moreover, pro-ENK is highly predictive of short-term mortality and could enable early identification of patients at risk of death.
authors.affiliation: Department of Medical Sciences and Translational Medicine, University of Rome Sapienza, Emergency Department Sant'Andrea Hospital, Via di Grottarossa 1035/1039, 00189, Rome, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Marino
authors.affiliation: Sphingotec GmbH, Hennigsdorf, Germany. struck@sphingotec.de.
authors.forename: Joachim
authors.initials: J
authors.lastname: Struck
authors.affiliation: Sphingotec GmbH, Hennigsdorf, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Hartmann
authors.affiliation: Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Maisel
authors.affiliation: Sphingotec GmbH, Hennigsdorf, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Rehfeldt
authors.affiliation: Department of Medical Sciences and Translational Medicine, University of Rome Sapienza, Emergency Department Sant'Andrea Hospital, Via di Grottarossa 1035/1039, 00189, Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Magrini
authors.affiliation: Department of Clinical Sciences, Lund University, Malmö, Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Melander
authors.affiliation: Sphingotec GmbH, Hennigsdorf, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bergmann
authors.affiliation: Department of Medical Sciences and Translational Medicine, University of Rome Sapienza, Emergency Department Sant'Andrea Hospital, Via di Grottarossa 1035/1039, 00189, Rome, Italy. salvatore.disomma@uniroma1.it.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Di Somma
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood* / Q000175:diagnosis* / Q000401:mortality; D000209:Acute-Phase Proteins; D000368:Aged; D000369:Aged, 80 and over; D003404:Creatinine / Q000097:blood / Q000652:urine; D004636:Emergency Service, Hospital; D004745:Enkephalins / Q000097:blood*; D005260:Female; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood; D008297:Male; D011237:Predictive Value of Tests; D011379:Prognosis; D011498:Protein Precursors / Q000097:blood*; D011518:Proto-Oncogene Proteins / Q000097:blood; D012189:Retrospective Studies; D018805:Sepsis / Q000097:blood* / Q000401:mortality; D013997:Time Factors
chemical_list: D000209:Acute-Phase Proteins; D004745:Enkephalins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011498:Protein Precursors; D011518:Proto-Oncogene Proteins; C029992:proenkephalin; D003404:Creatinine
keywords: Acute kidney injury; Enkephalin; Mortality; NGAL; RIFLE; Sepsis