腎不全状態におけるHemoglobin (Hb) A₁

尿素によるHbA₁の生成

抄録

Effects of renal failure on HbA_I levels were investigated.
Criteria for glucose intolerance with normal HbAI levels were determined: normal OGTT or borderline OGTT with FBS below 117mg/dl, peak BS below 223mg/dl and ΣBS below 980mg/dl. By these criteria 30 patients with non-hemodialysed, non-diabetic CRF were selected and their HbA_I levels were measured by ion-exchange column chromatography using Trivelli's method. HbA_I levels elevated in patients with BUN levels above 50mg/dl and correlated significantly with BUN (r=0.83, p<0.0001) and CRTN (r=0.57, p<0.001).
Red blood cells from normal subject were incubated for 5 days in 30mM triethanolamine HCl buffer, and HbA_I levels were determined. In medium containing 500mg/dl of urea N (containing tracer dosis of ¹⁴C-urea) and 100mg/dl of glucose, HbA_Ia+b, HbA_Ic and the leading edge of HbA_II increased markedly. HbA_Ia+b increased to 12.0% from 2.0%, and HbAIC to 19.2% from4.7%. ¹⁴C-urea was incorporated into HbA_Ia+b, HbA_Ic and the leading edge of HbA_II. The ratios of D. P. M./ml to optical density of each eluate, which might imply numbers of urea molecule per hemoglobin, were greater in HbA_Ia+b and HbA_Ic than in the leading edge of HbA_II. In media with urea N levels above 100mg/dl (100, 200, 300, 400 and 500) HbA_I levels correlated highly with urea concentrations (r=0.99, p<0.0001). Addition of other uremic toxins (CRTN, UA, MG, GAA, GSA and GPA) to the incubation media did not significantly increase HbA_I levels.
These findings suggest that urea induces the elevation of HbA_I levels due to the direct binding of urea to hemoglobin or due to the binding of cyanate, which is in equilibrium with urea in aqueous solution, and that HbA_Ia+b and HbA_Ic might bind more urea (or cyanate) molecules than the leading edge of HbA_II. In diabetic CRF patients, therefore, an incraese in HbA_I might be influenced not only by impaired glucose metabolism but also by high BUN levels.