Secretory activity and aryl acid content of serum, urine, and cerebrospinal fluid in normal and uremic man

Abstract

Serum from uremic human subjects causes net fluid secretion in proximal straight tubules isolated from rabbit kidneys in a manner similar to paraaminohippuric acid. In the present study, we determined the relation between the concentration of aryl acids (hippuric acid, benzoic acid, etc.) In serum, urine, and cerebrospinal fluid (CSF) and the capacity of the biologic fluids to cause fluid secretion in renal tubules. The concentration of aryl acids in serum and urine as estimated by fluorometric assay (Fl-Hipp) was related to the secretory activity (SA) estimated by bioassay in a direct linear fashion over a 10,000-fold range of concentrations. Fl-Hipp and SA were strikingly elevated in the serum of uremic patients. Hippuric acid determined by gas-liquid chromatography accounted for approximately one-fourth of the secretory activity of serum and urine; benzoic acid was present only in trace amounts; the remainder of the secretory activity of uremic serum is probably due to derivatives of aryl acids which are detected as Fl-Hipp. The relation between creatinine clearance and the SA or Fl-Hipp concentration of serum was hyperbolic; both the SA and Fl-Hipp content of serum increased sharply when creatinine clearance fell below 10 ml. per minute. The SA and Fl-Hipp content of CSF was increased in uremic patients; however, the serum content exceeded that of the CSF by more than fourfold suggesting an exclusion mechanism for aryl acids in the central nervous system. We conclude that the secretory activity of uremic serum is due to the accumulation of aryl acids, probably of the hippurate class, and, further, that relatively high levels of these biologically active substances may contribute to general organ dysfunction in uremia owing to their potential to act as competitive inhibitors of organic anion transport.