Role of protein-bound uremic toxins in the pathogenesis of chronic kidney disease

Chronic renal insufficiency is associated with the retention of solutes normally excreted by healthy kidneys. The compounds are called uremic toxins when they interact negatively with biological functions. In general, solutes that accumulate in the highest concentrations have been the most studied. But only a few compounds have been linked to toxic effects. The present review focuses on a specific class of molecules, namely the family of protein-bound uremic toxins. Recent experimental studies have shown that protein-bound toxins are involved not only in the progression of chronic kidney disease, but also in the generation and aggravation of cardiovascular disease. Two protein-bound uremic retention solutes, namely indoxyl sulfate and p-cresyl sulfate, have been shown to play a prominent role. However, although these two molecules belong to the same class of molecules, exert toxic effects on the cardiovascular system in experimental animals, and accumulate in the serum of patients with chronic kidney disease they may have different clinical impacts in terms of cardiovascular disease and other complications. Removal of these compounds by different dialysis strategies, even high-flux hemodialysis, is difficult, and only by applying convection, some improvement of removal has been obtained. The other strategy with the potential to decrease concentration is by influencing intestinal generation and/or absorption. The oral adsorbent Kremezin (AST-120) has been shown in controlled studies to decrease protein-bound solute concentration. The sorbent has the potential to delay dialysis initiation and improve survival of patients on dialysis.