Renal Transport of Diatrizoate in the Rabbit, Dog, and Rat

Abstract

The renal transport of ¹²⁵I-diatrizoate was examined in three species, dog, rabbit, and rat. In the rabbit this organic acid behaved like many such compounds, i.e. it was secreted by the proximal tubular organic anion process as judged by stop-flow analysis. The proximal tubular peak was abolished by probenecid. In vitro experiments with renal cortex slices gave results entirely consistent with the in vivo studies. Diatrizoate uptake by the slices was an energy-dependent, saturable process that was blocked by several organic acids known to be accumulated by the organic acid transport system. Rat renal cortex slices showed significant diatrizoate uptake, although of a lesser magnitude than noted with rabbit tissue (rat S/M = 1–2; rabbit S/M = 3–5). Except for the failure of acetate to stimulate diatrizoate uptake, accumulation by the rat slices appeared to be by the organic acid transport process. On the other hand, dog slices failed to accumulate diatrizoate. The process was not stimulated by acetate or any other metabolic substrate nor was it blocked by metabolic inhibitors or various organic acid competitors. No evidence of proximal tubular secretion was noted in the dog using stop-flow analysis; diatrizoate-inulin U/P ratios were approximately 0.9. Furthermore in p-amino-hippurate (PAH) clearance experiments in the dog, administration of diatrizoate failed to alter PAH clearance. These data indicate active renal transport of diatrizoate in certain species, but not in others.

Glomerular filtration and saturable absorption of iohexol in the rat isolated perfused kidney

“…The effect of probenecid was investigated, because the tubular titration curve for iohexol in the IPK diverged from the theoretical curve, and a secretory component may be involved in the renal clearance of iohexol. In addition, other investigators suggested previously that the reduced renal accumulation of the contrast analogue diatrizoate, determined after pretreatment with probenecid, was a result of inhibition of organic anion transport (Mudge et al, 1971). Contrary to these findings, probenecid enhanced the clearance of iohexol in our IPK preparations.…”

Effect of Dose on Renal Diatrizoate Concentrations in Experimental Acute Renal Failure

“…Although some tubular transport may occur at low doses [14,20,26,27] this becomes insignificant at doses used clinically. In the present study the upper half of our dose range covers the spectrum of clinical usage.…”

Diatrizoate Levels in the Kidney and Lymph Nodes in Acute Renal Failure in the Rat

“…If tubular secretion of diatrizoate occurs in man, the proportion excreted by this route appears to be small, even at low doses [10]. In the rat, in vitro experiments with slices of renal cortex suggest that tubular secretion of diatrizoate either does not occur [29] or is small in amount [25]. Though we administered diatrizoate at a dose lower than those employed in excretion urography, we consider it unlikely that secretion by normally functioning tubules accounts for the very much greater concentrations which we found in controls.…”

“…In the rat too, tubular secretion either does not occur [29] or is small in amount [25], In acute renal failure the appearance of a dense nephro gram immediately after intravenous injection of diatrizoate may indicate that glomerular filtration continues [6], In man the density of this nephrogram may be as great as it is in subjects with normal renal function [5], This suggests that glomerular filtration in acute renal failure is not significantly reduced. How ever, nephrographic density is difficult to quantify [6,11,15], and much ex-perimental work in acute renal failure appears to indicate that glomerular filtration is profoundly diminished [13,26,31].…”