Carbamylation describes a nonenzymatic posttranslational protein modification 
mediated by cyanate, a dissociation product of urea. When kidney function 
declines and urea accumulates, the burden of carbamylation naturally increases. 
Free amino acids may protect proteins from carbamylation, and protein 
carbamylation has been shown to increase in uremic patients with amino acid 
deficiencies. Carbamylation reactions are capable of altering the structure and 
functional properties of certain proteins and have been implicated directly in 
the underlying mechanisms of various disease conditions. A broad range of 
studies has demonstrated how the irreversible binding of urea-derived cyanate to 
proteins in the human body causes inappropriate cellular responses leading to 
adverse outcomes such as accelerated atherosclerosis and inflammation. Given 
carbamylation's relationship to urea and the evidence that it contributes to 
disease pathogenesis, measurements of carbamylated proteins may serve as useful 
quantitative biomarkers of time-averaged urea concentrations while also offering 
risk assessment in patients with kidney disease. Moreover, the link between 
carbamylated proteins and disease pathophysiology creates an enticing 
therapeutic target for reducing the rate of carbamylation. This article reviews 
the biochemistry of the carbamylation reaction, its role in specific diseases, 
and the potential diagnostic and therapeutic implications of these findings 
based on recent advances.