Phenylacetyglutamine (PAG) and hippuric acid (HA) were determined in protein-free filtrates of plasma and urine from patients with chronic renal failure and healthy subjects, using reverse phase high performance liquid chromatography. Plasma accumulation of the metabolites was detected when the creatinine clearance was below 15 ml/min. Protein-binding studies showed that PAG was not bound to plasma proteins but that HA was partly bound. Concentrations of PAG and free HA in plasma did not correlate with values of serum urea or creatinine. Hemodialysis decreased the plasma concentration of PAG and free HA to about the same extent as that of urea and creatinine. The average renal clearances of PAG and HA were about 1.4 and 5 times higher, respectively, than the creatinine clearance. The daily excretion rates of PAG, HA, urea, and creatinine were similar in non-dialysis patients with a creatinine clearance higher than 15 ml/min and in healthy subjects, whereas patients with a creatinine clearance below 15 ml/min had lower excretion rates of urea, creatinine, and HA. However, the average excretion rate of PAG was in the same range in uremic and healthy subjects. The excretion rate of HA, but not of PAG, correlated with that of urea and creatinine.

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