The Binding capacity of albumin and renal disease

Abstract

The capacity of albumin to bind the anionic dye, methyl orange, was determined in normal volunteers, in patients with renal failure and in patients after kidney transplantation in an attempt to elucidate the cause of the observed decreased albumin binding capacity for various drug and dye molecules in these patients. Binding studies were determined at 25°C, in a physiological bicarbonate carbon dioxide buffer system, ionic strength 0.15, using ultrafiltration and gel filtration techniques. Patients with renal failure bad lower albumin binding capacities than the normal volunteers and this reduction was generally unrelated to the degree of renal failure. The order of binding capacity being: patients with acute and chronic renal failure > patients before haemodialysis > patients after kidney transplantation > patients after haemodialysis. This reduction in binding was reflected in the downward displacement of the binding curves of pooled sera of each of the above groups of patients compared to that of normal volunteers. Each binding curve was analysed in terms of three classes of binding sites, and the reduced binding appeared to be due to an alteration in the n and K binding parameters of the intermediate class of sites. The reduced binding after dialysis was shown to be caused by competition by the temporarily increased concentration of non-esterified fatty acids as a result of lipoprotein-lipase activation by heparin administered during haemodialysis. The cause of the decreased binding of the other sera was not apparent, but could have been due to drug or metabolic product competition for the dye binding sites or due to a conformational change in the albumin molecule. The significance of this decreased binding capacity in relation to drug therapy in these patients is discussed.