Circulating Proenkephalin, Acute Kidney Injury, and Its Improvement in Patients with Severe Sepsis or Shock

Clin Chem. 2018 Sep;64(9):1361-1369. doi: 10.1373/clinchem.2018.288068. Epub 2018 Jul 16.


Background: Acute kidney injury (AKI) occurs in many critically ill patients and is associated with high mortality. We examined whether proenkephalin could predict incident AKI and its improvement in septic patients.

Methods: Plasma proenkephalin A 119-159 (penKid) was assayed in 956 patients with sepsis or septic shock enrolled in the multicenter Albumin Italian Outcome Sepsis (ALBIOS) trial to test its association with incident AKI, improvement of renal function, need for renal replacement therapy (RRT), and mortality.

Results: Median [Q1-Q3] plasma penKid concentration on day 1 [84 (20-159) pmol/L[ was correlated with serum creatinine concentration (r = 0.74); it was higher in patients with chronic renal failure and rose progressively with the renal Sequential Organ Failure Assessment subscore. It predicted incident AKI within 48 h (adjusted odds ratio, 3.3; 95% CI, 2.1-5.1; P < 0.0001) or 1 week [adjusted hazard ratio, 2.1 (1.7-2.8); P < 0.0001] and future RRT during the intensive care unit stay [odds ratio, 4.0 (3.0-5.4)]. PenKid was also associated with improvements in renal function in patients with baseline serum creatinine >2 mg/dL, both within the next 48 h [adjusted odds ratio, 0.31 (0.18-0.54), P < 0.0001] and 1 week [0.23 (0.12-0.45)]. The time course of penKid concentrations predicted AKI and 90-day mortality.

Conclusions: Early measurement and the trajectory of penKid predict incident AKI, improvement of renal function, and the need for RRT in the acute phase after intensive care unit admission during sepsis or septic shock. PenKid measurement may be a valuable tool to test early therapies aimed at preventing the risk of AKI in sepsis.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / blood*
  • Acute Kidney Injury / physiopathology
  • Aged
  • Enkephalins / blood*
  • Female
  • Humans
  • Kidney Function Tests
  • Male
  • Middle Aged
  • Protein Precursors / blood*
  • Sepsis / physiopathology*
  • Shock, Septic / physiopathology*
  • Survival Rate


  • Enkephalins
  • Protein Precursors
  • proenkephalin