Decreased clearance of uraemic and mildly carbamylated low-density lipoprotein.

Low-density lipoprotein (LDL) was in vitro carbamylated with potassium cyanate and the clearance was studied in man. A minor carbamylation of LDL decreased the clearance of LDL by 41% (94% of amino groups free) and by 18% (90% of amino groups free). When LDL was extensively carbamylated its clearance was substantially accelerated. Moreover, the clearance of LDL isolated from 14 haemodialysis patients (uremic-LDL) was studied in rabbits. Uraemic-LDL, injected into rabbits simultaneously with the LDL of a healthy control subject, was cleared more slowly than the control-LDL (difference in fractional catabolic rate -6.5%, P = 0.02). We also examined the lipid peroxidation of the carbamylated LDL by measuring the amount of thiobarbituric-acid reactive substances (TBARS) and formation of conjugated dienes during exposure of carbamylated LDL to 5 microM Cu2+. The carbamylated and native LDL had similar lipid peroxidation and propensity for oxidation. In summary, both the uraemic-LDL and minimally carbamylated LDL had a decreased clearance in vivo, which may contribute to the accelerated atherosclerosis in uraemic patients.