#5511 exploring the impact of potential uremic toxins in chronic kidney disease by proteomics: potential benefits or adverse effects?

Abstract Background and Aims Chronic kidney disease (CKD) is a progressive disorder characterized by a gradual reduction in kidney function. Proteomics, a large-scale analysis of protein modifications, has been used to study CKD and identify potential therapeutic targets. Studies have found that CKD is associated with changes in the expression of numerous proteins, including those involved in inflammation, cell adhesion, and metabolism. Additionally, proteomic studies have been used to identify potentially novel uremic toxins, which are compounds that accumulate in the body due to impaired kidney function. Method We performed a cross-sectional shotgun-proteomic study of pooled plasma across CKD stages and compared them to healthy controls. After sample pooling and heparin-column purification we analysed proteomes from healthy to CKD stage 1 through 5 participants’ plasma by liquid-chromatography/mass-spectrometry. Results Our results of proteomic profiling of the plasma of the patients with CKD1-5, including those after kidney transplantation, unequivocally showed that the key processing of the disease, regardless of the type and function of the observed protein groups, occurs in stage 2 of CKD, which we could call the stage - a tipping point. Through the analysis of 453 proteins, 7 established uremic toxins of "middle molecular mass" were identified. Further analysis was conducted to identify potential candidates for new uremic toxins, resulting in the identification of 15 novel proteins that may have a systemic inflammatory effect, atherogenic potential, or increase the risk of cardiovascular diseases. Conclusion These findings suggest that proteomics can be used to identify novel uremic toxins and provide new insights into the pathophysiology of CKD and selected toxins arrange by toxic, beneficial effect or both. Further research is needed to validate these findings and explore the potential therapeutic implications of targeting these uremic toxins.