Platelet/Leukocyte activation, inflammation, and uremia

Chronic kidney disease (CKD) is a state of chronic, low-grade inflammation which contributes to the accelerated progression of chronic inflammatory disturbances of which atherosclerosis is a major example. Platelet and leukocyte activation and interaction, evoked by the uremic condition, play an important role in this process. The effect of specific uremic retention solutes, progressively retained in uremia, on important platelet and leukocytes functions is discussed and summarized. The main uremic toxins involved are molecules with a molecular weight above 500 Da (the so-called "middle molecules") and/or protein-bound molecules. Classification of the molecules and elucidation of the pathophysiological pathways involved will result in new therapeutic strategies pursuing specific removal or pharmacological neutralization of molecular impact.