P1286THE RELATIONSHIP BETWEEN PROTEIN-BOUND UREMIC TOXINS AND TARGET CARDIOVASCULAR PROTEINS IN HEMODIALYSIS PATIENTS

Abstract

Abstract Background and Aims Uremic toxins are crucial non-traditional risk factors for cardiovascular disease in patients with chronic kidney disease (CKD). Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) were associated with all-cause and cardiovascular mortality in CKD patients, but possible mechanisms have not been fully elucidated. Herein, we explored the association between protein-bound uremic toxins and 181 cardiovascular-specific proteins in patients receiving hemodialysis (HD). Method In the discovery phase, we investigated associations between circulating free form IS and PCS and cardiovascular-specific protein levels quantified by a proximity extension assay of 333 stable HD patients with correction for multiple testing. In the second phase, the independent association was assessed using multivariable-adjusted models. The associations of IS or PCS with cardiovascular-specific proteins levels on a continuous scale were also evaluated. Results Free form IS was negatively associated with six proteins (C-C motif chemokine 15, complement component C1q receptor, perlecan, bleomycin hydrolase, cluster of differentiation 166 antigen, and signaling lymphocytic activation molecule family member 5) and positively associated with one protein (fibroblast growth factor 23). Free form PCS was negatively associated with three proteins (C-C motif chemokine 15, complement component C1q receptor, and interleukin-1 receptor-like 2). Adjusting the multivariable models for classical cardiovascular risk factors at baseline yielded similar results. Conclusion Protein-bound uremic toxins (IS and PCS) were associated with several cardiovascular-specific proteins involved in cell adhesion, endothelial barrier function, inflammation, complement system, and phosphate homeostasis. Multiplex proteomics appears to be a promising way to explore novel aspects of uremic toxin pathophysiology.