Impact of Circulating N-Acylethanolamine Levels with Clinical and Laboratory End Points in Hemodialysis Patients

BACKGROUND: Patients with end-stage renal disease (ESRD) on maintenance hemodialysis (MHD) are particularly susceptible to dysregulation of energy metabolism, which may manifest as protein energy wasting and cachexia. In recent years, the endocannabinoid system (ECS) has been shown to play an important role in energy metabolism with potential relevance in ESRD. N-acylethanolamines (NAEs) are a class of fatty acid amides which include the major endocannabinoid ligand, anandamide, and the endogenous peroxisome proliferator-activated receptor-α (PPAR-α) agonists, oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). METHODS: Serum concentrations of OEA and PEA were measured in MHD patients and their correlations with various clinical/laboratory indices were examined. Secondarily, we evaluated the association of circulating PEA and OEA levels with 12-month all-cause mortality. RESULTS: Both serum OEA and PEA levels positively correlated with HDL-C levels and negatively correlated with body fat and body anthropometric measures. Serum OEA levels correlated positively with serum interleukin-6 (IL-6) (rho=0.19, p=0.004). Serum PEA and IL-6 showed a similar but nonsignificant trend (rho= 0.12, p=0.07). Restricted cubic spline analyses showed that increasing serum OEA and PEA both trended towards higher mortality risk, and these associations were statistically significant for PEA (PEA≥4.7 pmol/mL, reference: PEA