Over a Perfusate Concentration Range of 5 -2 0 /¿g Ml 2 at a Concentration of 5 ¿¿g M L ' \ a Ratio of Renal Clearance over Clearance by Glomerular Ratio Mcreas 1.02 + 0.06 at /ig Ml

1 The renal handling of iohexol was examined in the rat isolated perfused kidney (IPK)-1 (C1r/GF) of 0.63 ± 0.06 could be indicating that a saturable mechanism is involved in the luminal disappearance of the drug. 3 Pretreatment of the kidneys with polylysine, probenecid or diatrizoate resulted in a significantly enhanced clearance o f iohexol, probably due to inhibition of membrane binding. Renal clearance data were fitted to a kinetic model including filtration into the primary urine followed by saturable absorption at the luminal membrane. An absorption constant, KA, of 7 .3 + 1 .3 /ig ml 1, and a maximum rate of absorption, FA.Max, ° f 1.4+ 0.1 /ig m in ~1 were determined. 4 Iohexol accumulated in kidney tissue, reaching a concentration of 2 to 7.5 times the perfusate concentration. In freshly isolated proximal tubular cells and kidney cortex mitochondria, iohexol reduced the uncoupled respiratory rate at a concentration comparable to the highest tissue concentration found in the IPK. 5 In conclusion, iohexol is not only filtered by the kidney but also reabsorbed via a saturable mechanism, which results in tubular accumulation. Intracellularly sequestered iohexol may affect mitochondrial oxidative metabolism. Our results indicate that iohexol is not a true filtration marker.