2.2.5. Carbamylation

The buildup of urea in CKD may drive the progression of disease via carbamylation [57]. Carbamylation is an irreversible nonenzymatic post-translational modification of proteins from the reaction between isocyanic acid and amino groups on lysine residues or the N-terminal extremity of proteins. Isocyanic acid derives mainly from spontaneous dissociation of urea into ammonia and cyanate (Figure 2). Cyanate is converted into its tautomer isocyanic acid, which is highly reactive and immediately binds to proteins and thus moves the equilibrium toward dissociation. The elevated levels of urea in CKD patients increases cyanate generation and therefore protein carbamylation. Isocyanic acid may also be formed from thiocyanate under the action of myeloperoxidase in the presence of hydrogen peroxide released by leukocytes in sites of inflammation. Carbamylated protein malfunction triggers unfavorable molecular and cellular responses and may accelerate the progression of kidney disease [57].
