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

Abstract

1 The renal handling of iohexol was examined in the rat isolated perfused kidney (IPK) over a perfusate concentration range of 5-20 Mg ml-'. 2 At a concentration of 5 Mg ml-', a ratio of renal clearance over clearance by glomerular filtration (CIR/GF) of 0.63 + 0.06 could be determined. This ratio increased until 1.02+0.06 at 20 Mg ml-, 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 of 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 Mg ml-', and a maximum rate of absorption, VA,MaX, of 1.4+0.1 Mg min-' were determined. 4 lohexol 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.

Iohexol Clearance for Determination of Glomerular Filtration Rate in Rats Induced to Acute Renal Failure

“…In such studies, the levels were underestimated when compared with those of inulin clearance. A potential explanation for this finding is the occurrence of the saturable tubular reabsorption of iohexol that has been documented in dogs in an in vitro perfusion study [ 24 ]. This species-specific peculiarity might explain the greater difference in the normal value ranges of the GFR (the CT animals) between iohexol vs. inulin.…”

Plasma Iohexol Clearance for Assessing Residual Kidney Function in Dialysis Patients

“…(8) Proximal tubular reabsorption of filtered iohexol has been described in animal models and may explain higher plasma versus urinary CL iohexol . (9) Measurement differences between plasma and urinary CL iohexol could also be due to a matrix effect (using an iohexol assay calibrated in plasma for urine samples). (10)…”