Jankowski V, Saritas T, Kjolby M, et al. - In chronic kidney disease (CKD), carbamylated sortilin (an intracellular sorting receptor) may not only confer risk for cardiovascular calcification but could also behave as a contributor to increased cardiovascular complications in patients.

• Specific CKD-induced posttranslational protein alterations of sortilin as well as their association with cardiovascular calcification were investigated.

• Two independent CKD cohorts were examined for carbamylation of circulating sortilin, and increased carbamylated sortilin lysine residues in the extracellular domain of sortilin with kidney function decline was identified.

• In vitro and ex vivo, an increase in vascular calcification due to carbamylated sortilin was observed that was accelerated by interleukin 6.

• Using mass spectrometry, human calcified arteries were studied and findings showed in situ carbamylated sortilin.

• A link of sortilin carbamylation with coronary artery calcification was found, which was independent of age and kidney function, in CKD patients.

• Significantly faster progression of coronary artery calcification was observed in patients with carbamylated sortilin vs those without sortilin carbamylation.