Proenkephalin predicts acute kidney injury in cardiac surgery patients

Clin Nephrol. 2015 Jan;83(1):29-35. doi: 10.5414/cn108387.


Aims: Acute kidney injury (AKI) occurs in up to 40% of patients undergoing cardiac surgery. Proenkephalin A 119-159 (pro-ENK) is a novel, stable surrogate biomarker for enkephalins, endogenous opioids involved in various physiological processes, including neurohormonal stress.

Material and methods: 92 patients undergoing cardiac surgery at the Veterans Affairs San Diego Healthcare System had a post-hoc analysis performed to determine the ability of pro-ENK to predict AKI as well as to compare it against other risk factors for development of AKI.

Results: Of 92 patients, 20 patients developed AKI post-operatively. Pro-ENK levels were significantly elevated in patients who develop AKI. Log pro-ENK value pre-operatively has an odds ratio of 23.8 (p = 0.011, 95% CI = 2 - 270) in its association with AKI. Pro-ENK performs similarly to baseline creatinine in its ability to predict post-operative AKI. Importantly, pro-ENK has a strong positive correlation with creatinine (r = 0.806). Additionally, changes in pro-ENK level, from pre-operatively to 12 hours post-operatively have greatest area under curve by ROC analysis for AKI after post-operative day 1.

Conclusion: Pro-ENK is associated with prediction of AKI in patients undergoing cardiac surgery. Pro-ENK likely has decreased clearance in the setting of AKI. However, future studies analyzing this novel biomarker should be considered to further elucidate its clinical utility and to better understand mechanisms of renal injury.

MeSH terms

  • Acute Kidney Injury / blood*
  • Acute Kidney Injury / diagnosis
  • Aged
  • Cardiac Surgical Procedures / adverse effects
  • Cardiac Surgical Procedures / methods*
  • Creatinine / blood
  • Enkephalins / blood*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prospective Studies
  • Protein Precursors / blood*
  • ROC Curve
  • Risk Factors


  • Enkephalins
  • Protein Precursors
  • proenkephalin
  • Creatinine