Excretion and accumulation of diatrizoate in the isolated perfused rat kidney

Abstract

The present study was designed to investigate the renal disposition of diatrizoate in the isolated perfused rat kidney (IPK). To the IPK, 5 different doses were added (between 1.13 and 44 mg), resulting in initial perfusate concentrations between 4.5 and 175 μg/ml. At all perfusate concentrations, the renal excretion rate of diatrizoate was significantly lower than the filtration rate, indicating that a reabsorptive mechanism is involved in renal diatrizoate handling. The ratio of diatrizoate clearance over GFR (Cl R/GF) was 0.67±0.04 at 4.5 μg/ml, and increased slightly to 0.76±0.03 at 175 μg/ml, suggesting that tubular reabsorption is mediated by a saturable mechanism. Accumulation of diatrizoate in kidney tissue was significantly reduced after preincubation of the perfused kidneys with the organic anion transport inhibitor probenecid, whereas renal clearance was not affected. At an initial perfusate concentration of 4.5 μg/ml a kidney-to-perfusate ratio (K/P-ratio) of 2.5±0.9 was found, which decreased to 1.3±0.2 after preincubation with probenecid. At a perfusate concentration of 47 μg/ml a K/P-ratio of 1.4±0.3 was determined, which increased significantly to 2.5±0.4 at a concentration of 175 μg/ml. We suggest that this unusual profile in concentration-dependent accumulation may be explained by a renal clearance mechanism for diatrizoate that consists of saturable reabsorption in conjunction with active tubular secretion.