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

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. CKD_eGFR was defined as development of eGFR <60 ml/min/1.73 m² and CKD_UAE 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 CKD_eGFR and 371 developed CKD_UAE. The association of pro-ENK with CKD_eGFR was modified by sex (P_interaction < 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 CKD_UAE risk (0.83; 0.58-1.20). CONCLUSIONS:High pro-ENK is associated with increased risk of CKD_eGFR in men, but not in women. No association of pro-ENK with CKD_UAE was observed. These results should be interpreted with caution, since residual confounding and potential overfitting of models could have influenced the results.

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