Studies on the modification of hormones in patients with renal failure and clinical evaluation

with reference to carbamylated ACTH and insulin

Abstract

It has been reported that hemoglobin Al (HbAl), which is increased in patients with renal failure, is formed by carbamylation of Hb by cyanic acid derived from urea. Carbamylation is a non:enzymatic and non-specific reaction and may occur at some amino groups of proteins other Hb and peptides. We previously reported that the levels of carbamylated plasma protein were elevated in patients with renal failure and the biological activity of carbamylated L-triiodothyronine (T₃) was reduced than that of T₃. In the present study, insulin and 1-24 ACTH were incubated with cyanic acid to prepare carbamylated insulin and carbamylated ACTH. The resultant carbamylated insulin and carbamylated ACTH was able to be identified by the new peaks which were different from insulin and ACTH on high performance liquid chromatography (HPLC). According to increase in the concentrations of cyanic acid and duration of incubation, the areas of these new peaks increased, respectively. Therf ore, it was considered that these new peaks could be regarded as those of carbamylated insulin and carbamylated ACTH. It is suspected that in patients with renal failure those hormones in the blood may be formed to be carbamylated following with resultant decreased biological activities as well as carbamylated T₃. This is important in considering the endocrine function in petients with renal failure.