Phenylacetylglutamine and Hippuric Acid in Uremic and Healthy Subjects

Abstract

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.

Clearance of amino acids by hemodialysis in argininosuccinate synthetase deficiency

“…The low dialysate concentration, low dialytic clearance, and decline in plasma concentration suggest that glycine conversion to hippuric acid may partially account for its reduction in plasma concentrations. Zimmerman et al 34 previously reported that phenylacetylglutamine and hippuric acid had dialytic clearances similar to urea and creatinine. The dialytic clearances and subsequent decline in plasma concentrations of glutamine and glycine may decrease ongoing production of phenylacetylglutamine and hippuric acid, respectively.…”

Altered microbiome in chronic kidney disease: systemic effects of gut-derived uremic toxins

“…Microbes metabolize phenylalanine to phenylacetic acid, which undergoes glutamine conjugation to form phenylacetylglutamine. Only ∼20% of phenylacetylglutamine is protein bound [40], thus, like TMAO it is dialyzable.…”

Microbiota-Derived Phenylacetylglutamine Associates with Overall Mortality and Cardiovascular Disease in Patients with CKD

“…17 Although p-cresyl sulfate and indoxyl sulfate are considered representatives of the group of protein-bound solutes caused by high protein binding, 18 PAG is much less protein bound, with a bound fraction of approximately 20%. 16,19 In general, it is often stated that protein binding limits solute removal by the native kidney as well as RRT, thus promoting accumulation and possibly, toxicity. 20 However, it can be assumed that only the free fraction of these solutes is biologically active and potentially harmful to the human body.…”