Nondialyzable uremic toxins

Nondialyzable uremic toxins can be defined as solutes producing adverse biological effects that consequently to peculiar physicochemical features (mainly their large size and hydrophobic character) cannot leave the blood stream through a dialysis membrane. These are the subject of great interest for the scientific community, in that emerging evidence suggests that such uremic retention solutes may contribute a main role to the complex inflammatory and vascular comorbidity of the uremic syndrome. Treatments based on most efficient diffusive or convective protocols of dialysis and pharmacological therapies cannot prevent nor correct such clinical symptoms. Protein-bound solutes and other proteinaceous components present in excess in the uremic milieu are thus natural candidates for explaining the resistance of uremic toxicity to current regimens of therapy. Intense research is in progress to identify molecular species and mechanisms of toxicity, but the real challenge of our times is to develop innovative clinical protocols that may remove or prevent the formation/toxicity of nondialyzable uremic solutes. These include high-efficacy protein-leaking dialyzers, adsorption techniques, frequent dialysis, and pharmacological therapies. These aspects are examined in this review paper, paying particular attention to covalent posttranslational modifications of plasma proteins produced as a consequence of oxidative, nitrosative and carbonyl stress. These represent an emerging trait in the pathobiology of inflammatory and age-related disorders, deserving further consideration in chronic kidney disease.