Identification of some abnormal metabolites in plasma from uremic subjects

We describe a method for comparing plasma samples from healthy subjects and from chronic uremic patients before and after dialysis. It was used to determine the nature of those metabolites that appear to characterize the uremic state. Preliminary fractionation of the metabolites by gel chromatography was followed by removal of the aqueous effluent by lyophilization and preparation of volatile trimethylsilyl derivatives, which were then examined by gas-liquid chromatography. Gas-liquid chromatography/mass spectrometry was used to characterize and identify individual metabolites. Gas-liquid chromatographic patterns of plasma from healthy and uremic subjects differ markedly, more so than do individual plasma samples within the same class of subjects. Concentrations of many metabolites are increased in uremia, but after dialysis of the patient's blood, the concentrations become about the same as those in healthy plasma. We have observed some 150-200 metabolites in each category of plasma. We have tentatively identified about a tenth of the compounds that appear to be specific to or increased in uremia, including lactic acid, glycerol, erythritol, erythronic acid, 2-deoxy erythro pentonic acid, arabinitolarabinonic acid, inositol, and lactose. Some of these are present in concentrations greater than 20 mg/liter and have not been previously reported as occurring in the uremic state.