Proenkephalin for the early detection of acute kidney injury in hospitalized patients with chronic kidney disease

Eur J Clin Invest. 2018 Oct;48(10):e12999. doi: 10.1111/eci.12999. Epub 2018 Aug 6.


Background: The early detection of acute kidney injury (AKI) in patients with chronic kidney disease (CKD) is an unmet clinical need. Proenkephalin (PENK) might improve the early detection of AKI.

Methods: One hundred and eleven hospitalized CKD patients undergoing radiographic contrast procedures were enrolled. PENK was measured in a blinded fashion at baseline (before contrast media administration) and on day 1 (after contrast media administration). The potential of PENK levels to predict contrast-induced AKI was the primary endpoint.

Results: Baseline creatinine and baseline PENK were similar in AKI and no-AKI patients. In AKI patients, day 1 PENK (198 pmol/L vs 121 pmol/L, P < 0.01) was significantly higher compared to no-AKI patients. The area under the curve (AUC) for the prediction of AKI by day 1 PENK was 0.79, 95% CI: 0.70-0.87, similar to serum creatinine: 0.78, 95% CI: 0.61-0.95. Delta PENK was significantly higher in AKI compared to no-AKI patients (53 pmol/L vs 1 pmol/L, P < 0.01). The AUC for the prediction of AKI by delta PENK was high (0.92, 95%CI 0.82-1.00) and remained high for creatinine-blind AKI (0.94, 95% CI: 0.87-0.97).

Conclusion: Delta PENK levels improve the early detection of contrast-induced AKI in CKD patients over serial creatinine sampling. Delta PENK accelerates the detection of creatinine-blind AKI by 24 hours.

Keywords: acute kidney injury; chronic kidney disease; early detection; proenkephalin; sensitivity; specificity.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / diagnosis*
  • Aged
  • Aged, 80 and over
  • Area Under Curve
  • Biomarkers / metabolism
  • Contrast Media / adverse effects*
  • Creatinine / metabolism
  • Early Diagnosis
  • Enkephalins / metabolism*
  • Female
  • Hospitalization
  • Humans
  • Isotonic Solutions / administration & dosage
  • Male
  • Prospective Studies
  • Protein Precursors / metabolism*
  • Renal Insufficiency, Chronic / complications*
  • Sodium Bicarbonate / administration & dosage
  • Sodium Chloride / administration & dosage


  • Biomarkers
  • Contrast Media
  • Enkephalins
  • Isotonic Solutions
  • Protein Precursors
  • proenkephalin
  • Sodium Chloride
  • Sodium Bicarbonate
  • Creatinine