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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

Marino, Rossella; Struck, Joachim; Hartmann, Oliver; Maisel, Alan S.; Rehfeldt, Miriam; Magrini, Laura; Melander, Olle LU ; Bergmann, Andreas and Di Somma, Salvatore (2015) In Journal of Nephrology 28(6). p.717-724
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... (More)
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 chi(2) 10.0, p = 0.0016). Admission pro-ENK outperformed creatinine clearance in predicting 7-day mortality (pro-ENK: chi(2) 13.4, p < 0.001, area under curve, AUC 0.69; creatinine clearance: chi(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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Mortality, NGAL, RIFLE, Sepsis, Acute kidney injury, Enkephalin
in
Journal of Nephrology
volume
28
issue
6
pages
717 - 724
publisher
Springer
external identifiers
  • wos:000363037900008
  • scopus:84944195742
ISSN
1724-6059
DOI
10.1007/s40620-014-0163-z
language
English
LU publication?
yes
id
30ae9b7c-cae8-4f70-bf78-c6c5ebd33495 (old id 8195176)
date added to LUP
2015-11-26 09:25:43
date last changed
2017-09-17 04:01:11
@article{30ae9b7c-cae8-4f70-bf78-c6c5ebd33495,
  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 &lt; 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 chi(2) 10.0, p = 0.0016). Admission pro-ENK outperformed creatinine clearance in predicting 7-day mortality (pro-ENK: chi(2) 13.4, p &lt; 0.001, area under curve, AUC 0.69; creatinine clearance: chi(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.},
  author       = {Marino, Rossella and Struck, Joachim and Hartmann, Oliver and Maisel, Alan S. and Rehfeldt, Miriam and Magrini, Laura and Melander, Olle and Bergmann, Andreas and Di Somma, Salvatore},
  issn         = {1724-6059},
  keyword      = {Mortality,NGAL,RIFLE,Sepsis,Acute kidney injury,Enkephalin},
  language     = {eng},
  number       = {6},
  pages        = {717--724},
  publisher    = {Springer},
  series       = {Journal of Nephrology},
  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},
  url          = {http://dx.doi.org/10.1007/s40620-014-0163-z},
  volume       = {28},
  year         = {2015},
}