Accumulation of indoxyl sulfate, an inhibitor of drug-binding, in uremic serum as demonstrated by internal-surface reversed-phase liquid chromatography.

Abstract

Abstract We quantified indoxyl sulfate in uremic serum by using internal-surface reversed-phase high-performance liquid chromatography. Its concentrations were markedly increased in chronic hemodialysis patients, and were significantly but weakly correlated with the concentrations of creatinine and beta 2-microglobulin in these patients' serum, and with the duration of their hemodialysis treatment. Indoxyl sulfate could not be removed effectively by conventional hemodialysis because of its strong binding to serum albumin. Equilibrium dialysis demonstrated that indoxyl sulfate inhibited the binding of salicylate to albumin, and that 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid inhibited the binding of indoxyl sulfate to albumin. In conclusion, indoxyl sulfate was markedly accumulated in uremic serum, and inhibited drug binding.