Renal concentration gradients of salicylic acid and its metabolic congeners in the dog.

Salicylic acid and its principal metabolic product, salicyluric acid, are ultrafiltered at the glomeruli, secreted by the proximal segment and undergo back diffusion; the net effect being an accumulation of salicylates in the cortex. The back diffusion of salicylate is pH-sensitive (salicylurate is not) and its secretion is less sensitive than that of salicylurate to depression by probenecid. There was an increasing concentration gradient of these salicylates from outer cortex to innermost medulla. The clearance of salicyluric acid exceeded glomerular filtration rate even at very low urine flow and was not pH-dependent, so that total salicylate accumulation in the medulla was less affected by adjustment of urinary pH. Increasing perfusion of the nephron markedly reduced the inner medulla/cortical concentration ratios and segmental concentrations of salt and urea and reduced the cortical concentrations of salicylates. Diuresis may decrease the medullary concentration of salicylates, depending on the rate and duration of increased urine flow.