Kynurenine and its metabolites--kynurenic acid and anthranilic acid are associated with soluble endothelial adhesion molecules and oxidative status in patients with chronic kidney disease.

BACKGROUND

Cellular adhesion molecules and oxidative stress play a role in the pathogenesis of atherosclerosis in patients with chronic kidney disease (CKD). Recently, it has been postulated that the kynurenine (KYN) pathway could be involved in the pathogenesis of atherosclerosis.

METHODS

We evaluated the KYN, kynurenic acid (KYNA), anthranilic acid (AA), and their relations with cellular adhesion molecules: soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), sE-selectin, sP-selectin, and Cu/Zn superoxide dismutase (Cu/Zn SOD) levels as the markers of oxidative stress in the population of 132 patients with CKD and 28 healthy controls.

RESULTS

Compared with the controls, 2 groups of dialyzed patients had significantly increased KYN (both P < 0.01), KYNA, AA, sICAM-1, sVCAM-1, and Cu/Zn SOD levels (all P < 0.001, respectively). KYN, AA, sICAM-1, and sVCAM-1 concentrations were significantly higher in undialyzed patients with CKD compared with healthy subjects (P < 0.001, P < 0.01, and both P < 0.05, respectively). sICAM-1 and sVCAM-1 were positively associated with KYN (P < 0.0001 and P < 0.01), KYNA (P < 0.05 and P < 0.0001), AA (P < 0.01 and P < 0.0001), and with Cu/Zn SOD (both P < 0.0001, respectively) in the whole CKD group. The positive relationship existed between sICAM-1, sVCAM-1 and age, high-sensitivity C-reactive protein, creatinine, and the duration of dialysis therapy. Multivariable analysis showed that KYN was a strong independent correlate of sICAM-1, whereas Cu/Zn SOD and platelets independently and significantly predicted sVCAM-1 in patients with CKD.

CONCLUSIONS

This study demonstrated that KYN is independently and significantly associated with elevated sICAM-1, whereas oxidative status and platelets independently and significantly predicted increased sVCAM-1 levels in patients with CKD.