Decreased bilirubin-binding capacity in uremic serum caused by an accumulation of furan dicarboxylic acid

In chronic renal failure, substances that are effectively excreted in healt hy subjects accumulate in serum, These substances, uremic toxins, include a variety of organic acids, It has been reported that a decrease in the bili rubin (BR) binding capacity occurs in the serum of renal failure patients. 3-Carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) has a high affinit y for hu man serum albumin (HSA) and is a potent inhibitor of the serum pro tein binding of many drugs. We recently reported that CMPF and BR share the binding site for dicarboxylate molecules on the HSA molecule [Pharm Res 19 99;16:916-923], In this study, in order to confirm whether CMPF is involved in the decrease of BR serum binding capacity in chronic renal failure pati ents, the total concentrations of uremic toxins, CMPF, and indoxyl sulfate (IS) and the free BR concentration in serum from healthy volunteers and ren al failure patients were determined. Both total CMPF and IS concentrations correlate with the free BR concentration. However, results from the peroxid ase method reveal that IS cannot displace BR under the physiological condit ion [IS]/[HSA] <1. We, therefore, conclude that CMPF is one of the substanc es which contribute to the decreased binding capacity of BR in uremic serum , Copyright (C) 2000 S. Karger AG, Basel.