The value of a low-protein diet and ketoanalogues of essential amino acids in the сontrol of protein carbamylation and toxic effects of urea in chronic kidney disease

Abstract

Chronic kidney disease (CKD) is characterized by high mortality from cardiovascular diseases, the development of which is facilitated by traditional risk factors (typical for the general population) and by nontraditional ones (specific to patients with CKD) as well. These factors include also uremic toxins, for which a causal relationship has been established with specific pathological processes in patients with CKD, comprising the development of vascular dysfunction and accelerated progression of atherosclerosis. Urea has long been considered not as a uremic toxin, but as a marker of metabolic imbalance or dialysis efficiency (Kt/V) in CKD patients. In recent years, more and more publications have appeared on the study of the toxic effects of urea with the development of toxic-uremic complications and the phenotype of premature aging, common in CKD. It was found that an increase in urea levels in uremic syndrome causes damage to the intestinal epithelial barrier with translocation of bacterial toxins into the bloodstream and the development of systemic inflammation, provokes apoptosis of vascular smooth muscle cells, as well as endothelial dysfunction, which directly contributes to the development of cardiovascular complications. The indirect effects of increased urea levels are associated with carbamylation reactions, when isocyanic acid (a product of urea catabolism) changes the structure and function of proteins in the body. Carbamylation of proteins in CKD patients is associated with the development of renal fibrosis, atherosclerosis and anemia. Thus, urea is now regarded as an important negative agent in the pathogenesis of complications in CKD. Studies on a low-protein diet with using ketoanalogues of essential amino acids to minimize the accumulation of urea and other uremic toxins demonstrate the clinical benefit of such an intervention in slowing the progression of CKD and the development of cardiovascular complications.