Proenkephalin as a new biomarker for pediatric acute kidney injury - reference values and performance in children under one year of age

Clin Chem Lab Med. 2020 Oct 25;58(11):1911-1919. doi: 10.1515/cclm-2020-0381.


Objectives Acute kidney injury (AKI) is common in critically ill children, but current biomarkers are suboptimal. Proenkephalin A 119-159 (PENK) is a promising new biomarker for AKI in adults, but pediatric data is lacking. We determined PENK reference intervals for healthy children, crucial for clinical implementation, and explored concentrations in critically ill infants aged under 1 year. Methods Observational cohort study in healthy infants and critically ill children aged 0-1 years. Reference values were determined using generalized additive models. Plasma PENK concentrations between healthy children and critically ill children with and without AKI, were compared using linear mixed modelling. The performance of PENK as AKI biomarker was compared to cystatin C (CysC) and β-trace protein (BTP) using receiver-operating-characteristic (ROC) analysis. Results PENK concentrations in 100 healthy infants were stable during the first year of life (median 517.3 pmol/L). Median PENK concentrations in 91 critically ill children, were significantly higher in those with AKI (n=40) (KDIGO Stage 1 507.9 pmol/L, Stage 2 704.0 pmol/L, Stage 3 930.5 pmol/L) than non-AKI patients (n=51, 432.2 pmol/L) (p < 0.001). PENK appeared to relate better to AKI diagnosis than CysC and BTP (AUROC PENK 0.858, CysC 0.770 and BTP 0.711) in the first 24 h after recruitment. Conclusions PENK reference values are much higher in young infants than adults, but clearly discriminate between children with and without AKI, with comparable or better performance than CysC and BTP. Our results illustrate the importance of establishing age-normalized reference values and indicate PENK as a promising pediatric AKI biomarker.

Keywords: acute kidney injury; biomarkers; pediatrics; proenkephalin; reference values.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / blood
  • Acute Kidney Injury / diagnosis*
  • Area Under Curve
  • Biomarkers / blood
  • Cohort Studies
  • Enkephalins / blood*
  • Female
  • Humans
  • Immunoassay / statistics & numerical data
  • Infant
  • Infant, Newborn
  • Male
  • Peptide Fragments / blood*
  • Protein Precursors / blood*
  • ROC Curve
  • Reference Values


  • Biomarkers
  • Enkephalins
  • Peptide Fragments
  • Protein Precursors
  • proenkephalin