Carbamylation and Cardiovascular Implications in Chronic Kidney Disease

Carbamylation is a non-enzymatic post-translational modification in which cyanate, derived from elevated urea levels in chronic kidney disease (CKD), binds to free amino groups of proteins. This irreversible alteration affects circulating and tissue proteins, including collagen, elastin and lipoproteins, leading to structural and functional changes. In CKD, accumulation of carbamylated proteins has been linked to endothelial dysfunction, extracellular matrix remodelling, arterial stiffening, pro-thrombotic clot formation and vascular calcification. These processes collectively contribute to heightened cardiovascular morbidity and mortality in CKD populations. Mechanistic and clinical studies underscore carbamylation as both a robust biomarker and a potential therapeutic target, with implications for risk stratification and the design of interventions aimed at reducing cardiovascular complications in renal impairment.

Research from Nature Portfolio

Recent studies have demonstrated that in conditions favouring both glycation and carbamylation, carbamylation of collagen predominates, thereby limiting glycation-derived cross-links and altering the mechanical properties of the vascular matrix. Complementary investigations into aortic elastic fibres have confirmed in vivo carbamylation of elastin, showing that this modification increases fibre stiffness at the molecular level and elevates aortic pulse wave velocity. These findings directly link protein carbamylation to arterial stiffening, a critical determinant of cardiovascular risk in patients with CKD.

Carbamylation and Cardiovascular Implications in Chronic Kidney Disease publication trend

The graph below shows the total number of articles in carbamylation and cardiovascular implications in chronic kidney disease across all publications each year (not limited to Nature Index journals).

Technical terms

Carbamylation: Non-enzymatic modification of proteins by cyanate that alters their charge, structure and function.

Cyanate: Reactive species formed by spontaneous dissociation of urea, responsible for driving protein carbamylation.

Homocitrulline: Biomarker of protein carbamylation formed when lysine residues are modified by cyanate.

Extracellular matrix: Network of proteins and polysaccharides providing structural support, which is susceptible to carbamylation in CKD.

Vascular calcification: Pathological deposition of calcium phosphate in blood vessel walls, contributing to arterial stiffness and cardiovascular risk.

References

1. Chronic Increase of Urea Leads to Carbamylated Proteins Accumulation in Tissues in a Mouse Model of CKD. PLOS ONE (2013).
2. Carbamylation and glycation compete for collagen molecular aging in vivo. Scientific Reports (2019).
3. Carbamylation of elastic fibers is a molecular substratum of aortic stiffness. Scientific Reports (2021).
4. Impact of fibrinogen carbamylation on fibrin clot formation and stability. Thrombosis and Haemostasis (2017).
5. Carbamylated Low-Density Lipoprotein (cLDL)-Mediated Induction of Autophagy and Its Role in Endothelial Cell Injury. PLOS ONE (2016).
6. Carbamylated sortilin associates with cardiovascular calcification in patients with chronic kidney disease. Kidney International (2021).