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

• Published in: Biomarkers Vol. 23; no. 5; pp. 474 - 482
• Main Authors: Kieneker, Lyanne M, Hartmann, Oliver, Bergmann, Andreas, de Boer, Rudolf A, Gansevoort, Ron T, Joosten, Michel M, Struck, Joachim, Bakker, Stephan J L
• Format: Journal Article
• Language: English
• Published: England 04.07.2018
• Subjects: epidemiology; Biomarker; chronic kidney disease
• ISSN: 1354-750X; 1366-5804
• DOI: 10.1080/1354750X.2018.1443514

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. We included 4375 subjects of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study. CKD was defined as development of eGFR <60 ml/min/1.73 m and CKD as albuminuria >30 mg/24 h. 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 CKD and 371 developed CKD . The association of pro-ENK with CKD was modified by sex (P  < 0.1), in such a way that after adjustment, the association only remained significant in men (adjusted hazard ratio per SD increase in log-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 CKD risk (0.83; 0.58-1.20). High pro-ENK is associated with increased risk of CKD in men, but not in women. No association of pro-ENK with CKD was observed. These results should be interpreted with caution, since residual confounding and potential overfitting of models could have influenced the results.