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Counteracting Carbamylation: A Possible Route to Treating Complications of Kidney Failure
Like a canary in a coal mine, too much glycated hemoglobin in the blood is a warning sign that a diabetic patients’ glucose is out of control. Carbamyl groups on another ubiquitous blood protein, albumin, may sound a similar alarm for blood urea, a consequence of failing kidneys. Carbamylation may be harmful in its own right because it has been linked to atherosclerosis and other diseases.
By using mass spectroscopy, the authors devised a highly accurate assay for measuring carbamylation of the lysine at position 549 of human albumin. With this assay, they found that in two groups of patients with end-stage renal disease and elevated blood urea, the amount of carbamylated albumin correlated with urea concentrations. Albumin was more carbamylated in patients with end-stage renal disease who died within a year than in those who lived longer.
Although knowing the prognosis of patients with kidney failure would let us prioritize transplants for the most needy, it would be even better if we could prevent the complications of kidney failure altogether. The authors have gathered data from biochemical experiments and from mice that suggest that protein carbamylation and its associated pathology might be prevented by boosting amino acid concentrations (which tend to be low in these patients) in the blood through diet or other means. Amino acids can compete with protein side chains during carbamylation, potentially interfering with the reaction and its harmful consequences. Thus, amino acid replacement might help patients with kidney failure.
- Copyright © 2013, American Association for the Advancement of Science
