Proenkephalin Predicts Organ Failure, Renal Replacement Therapy, and Mortality in Patients With Sepsis

Ann Lab Med. 2020 Nov;40(6):466-473. doi: 10.3343/alm.2020.40.6.466. Epub 2020 Jun 17.


Background: Kidney failure occurs frequently and is associated with high mortality during sepsis. Proenkephalin (PENK) is an emerging biomarker of kidney function. We explored whether PENK levels could predict severity, organ failure, and mortality in septic patients.

Methods: We measured the PENK level in the plasma of 215 septic patients using the sphingotest penKid assay (Sphingotec GmbH, Hennigsdorf, Germany). This was analyzed in terms of sepsis severity, vasopressor use, 30-day mortality, sequential organ failure assessment (SOFA) renal subscore, the Chronic Kidney Disease Epidemiology Collaboration estimated glomerular filtration rate (CKD-EPI eGFR) categories, and renal replacement therapy (RRT) requirement.

Results: The PENK levels were significantly higher in patients with septic shock, vasopressor use, and non-survivors than in patients with solitary sepsis, no vasopressor use, and survivors, respectively (P=0.02, P=0.007, P<0.001, respectively). The PENK levels were significantly associated with SOFA renal subscore and CKD-EPI eGFR categories (both P<0.001). The distribution of lower eGFR (<60 mL/min/1.73 m2), RRT requirement, SOFA renal subscore, and the number of organ failures differed significantly according to the PENK quartile (P for trend<0.001 or 0.017). The 30-day mortality rate also differed significantly according to the PENK quartile (P for trend<0.001).

Conclusions: PENK could be an objective and reliable marker to predict severity, organ failure, and 30-day mortality in septic patients.

Keywords: Kidney function; Mortality; Organ failure; Proenkephalin; SOFA score; Sepsis.

MeSH terms

  • Aged
  • Biomarkers / blood
  • Enkephalins / blood*
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multiple Organ Failure / complications
  • Multiple Organ Failure / pathology*
  • Proportional Hazards Models
  • Protein Precursors / blood*
  • Reagent Kits, Diagnostic
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / pathology*
  • Sepsis / mortality
  • Sepsis / pathology*
  • Shock, Septic / complications
  • Shock, Septic / mortality
  • Shock, Septic / pathology


  • Biomarkers
  • Enkephalins
  • Protein Precursors
  • Reagent Kits, Diagnostic
  • proenkephalin