Proenkephalin and risk of developing chronic kidney disease: the Prevention of Renal and Vascular End-stage Disease study

Biomarkers. 2018 Jul;23(5):474-482. doi: 10.1080/1354750X.2018.1443514. Epub 2018 Mar 8.


Background: Proenkephalin (pro-ENK) was recently found to be associated with low estimated glomerular filtration rate (eGFR). The association of pro-ENK with urinary albumin excretion (UAE), another marker for chronic kidney disease (CKD), has not been investigated. We examined the association of pro-ENK with eGFR and UAE as markers of CKD.

Methods: We included 4375 subjects of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study. CKDeGFR was defined as development of eGFR <60 ml/min/1.73 m2 and CKDUAE as albuminuria >30 mg/24 h.

Results: Baseline median pro-ENK was 52.2 (IQR: 44.9-60.5) pmol/L. After a median follow-up of 8.4 (IQR: 7.9-8.9) years, 183 subjects developed CKDeGFR and 371 developed CKDUAE. The association of pro-ENK with CKDeGFR was modified by sex (Pinteraction < 0.1), in such a way that after adjustment, the association only remained significant in men (adjusted hazard ratio per SD increase in 10log-transformed pro-ENK, 1.65; 95% CI: 1.15-2.36) and not in women (0.83; 0.58-1.20). No significant association was observed between pro-ENK and CKDUAE risk (0.83; 0.58-1.20).

Conclusions: High pro-ENK is associated with increased risk of CKDeGFR in men, but not in women. No association of pro-ENK with CKDUAE was observed. These results should be interpreted with caution, since residual confounding and potential overfitting of models could have influenced the results.

Keywords: Biomarker; chronic kidney disease; epidemiology.

MeSH terms

  • Adult
  • Aged
  • Albuminuria*
  • Biomarkers / urine
  • Enkephalins / analysis*
  • Female
  • Glomerular Filtration Rate*
  • Humans
  • Male
  • Middle Aged
  • Protein Precursors / analysis*
  • Renal Insufficiency, Chronic / diagnosis*
  • Sex Factors


  • Biomarkers
  • Enkephalins
  • Protein Precursors
  • proenkephalin