The Role of Downstream Kynurenine Pathway Metabolites in the Modulation of Cardiovascular Disease Development in Chronic Kidney Disease.

Cardiovascular diseases (CVDs) represent a significant and escalating health challenge in patients with chronic kidney disease (CKD). In this population, the cardiovascular incidents are markedly elevated, and CVD represents the leading cause of mortality. The pathogenesis of CVD in the course of CKD is multifactorial, and some evidence indicates that disturbances in the kynurenine pathway (KP), the major route of tryptophan metabolism, can also play a significant role in this process. The enhanced activation of the KP and reduced clearance of its metabolites contribute to their accumulation during CKD progression, potentially exacerbating cardiovascular risk. Few data suggest that certain downstream KP metabolites, including 3-hydroxykynurenine (3-HKYN), quinolinic acid (QUIN), and anthranilic acid (AA), are associated with established CVD risk factors, while others, such as 3-hydroxyanthranilic acid (3-HAA) and kynurenic acid (KYNA), exhibit more complex and ambiguous effects, with potential protective actions on the cardiovascular system. The aim of this review is to summarize current knowledge of the roles of individual downstream kynurenine (KYN) metabolites in the development of CVD in the CKD population. Since for some kynurenines there are only isolated or ambiguous reports in this field, the review has been completed with data on the contribution of downstream KYN metabolites in the development of CVD in the general population and in experimental models.