Relationship between an increased serum kynurenine/tryptophan ratio and atherosclerotic parameters in hemodialysis patients

Abstract

Essential amino acid tryptophan (Trp) is mainly catabolized by indoleamine 2,3-dioxygenase, which leads to the formation of kynurenine (Kyn). In this study, we reexamined whether an increased indoleamine 2,3-dioxygenase activity, as estimated by the Kyn/Trp ratio (μM/mM), is associated with atherosclerotic parameters in hemodialysis (HD) patients. Serum Trp and Kyn were measured in 243 HD patients by liquid chromatography/electrospray ionization tandem mass spectrometry. We measured carotid artery intima-medial thickness, brachial-ankle pulse wave velocity, ankle-brachial pressure index, and the cardio-ankle vascular index. Log-transformed Kyn/Trp ratio was significantly correlated with log-transformed time on HD (ρ=0.28, P<0.01), log-transformed highly sensitive C-reactive protein (ρ=0.20, P<0.01), and peripheral total lymphocyte count (ρ=-0.13, P<0.05). A significant association was found between log-transformed Kyn/Trp ratio and mean carotid artery intima-medial thickness (ρ=0.18, P<0.01). Mean carotid artery intima-medial thickness was significantly higher in the lowest quartile of Kyn/Trp ratio (<165) (0.62±0.12 mm) when compared with the highest quartile (≥304) (0.68±0.15 mm) (P<0.01). Ankle-brachial pressure index was lower in the second quartile (1.01±0.20), the third quartile (1.01±0.19), and the fourth quartile (1.03±0.15) compared with that in the first quartile (1.09±0.13) (P<0.05). It follows from these findings that the Kyn/Trp ratio increases with time on HD, and is associated with advanced atherosclerotic changes in chronic HD patients.