Characteristics of renal p-aminohippurate and urate excretion in rabbits

Urate and p-aminohippurate (PAH) excretion was studied in New Zealand white rabbits to determine the extent to which the renal tubular handling of these organic anions by intact kidneys paralleled observations made in single isolated perfused tubules in vitro. At low plasma concentrations (less than 60 mumol/L) net reabsorption of urate was observed in the majority of animals; as plasma urate concentration was increased by infusing lithium urate, net urate secretion was demonstrated, the fractional excretion of urate (FE urate) reaching 270%, and net urate secretion (filtered urate minus urinary concentration of urate times volume flow rate) 1.8 mumol/min at mean plasma urate levels 200 and 310 mumol/L. A maximal urate secretion rate was not demonstrated. Probenecid (250 mumol/kg) reduced FE urate to 27%, thereby revealing concealed reabsorption despite high plasma urate levels. By contrast, net secretion of PAH at all plasma levels was achieved by infusing NaPAH. The highest secretory rate was 38.6 mumol/min at plasma PAH levels between 1000 and 1750 mumol/L. Probenecid reduced fractional excretion of PAH (FEPAH) from 796% to 265%, no evidence of PAH reabsorption being found after inhibition of secretion with probenecid. At comparable plasma levels (220 mumol/L), net PAH secretion exceeded net urate secretion (reflected by the decrement in urate and PAH excretion caused by probenecid) by a factor of 5.3:1. These experiments indicate that urate and PAH are filtered and secreted by the rabbit kidney; however, only urate is significantly reabsorbed over the range of plasma organic anion levels examined. The configuration of the relation between plasma levels and net secretion rates and the greater secretory rate for PAH for urate in the living rabbit are consonant with the characteristics of PAH and urate transport determined previously in studies of isolated perfused proximal tubules.