GLOMERULAR-FILTRATION AND SATURABLE ABSORPTION OF IOHEXOL IN THE RAT ISOLATED-PERFUSED KIDNEY

1 The renal handling of iohexol was examined in the rat isolated perfu sed kidney (IPK) over a perfusate concentration range of 5-20 mu g ml( -1). 2 At a concentration of 5 mu g ml(-1), a ratio of renal clearance over clearance by glomerular filtration (Cl-R/GF) of 0.63+/-0.06 coul d be determined. This ratio increased until 1.02+/-0.06 at 20 mu g ml( -1), indicating that a saturable mechanism is involved in the luminal disappearance of the drug. 3 Pretreatment of the kidneys with polylysi ne, probenecid or diatrizoate resulted in a significantly enhanced cle arance of iohexol, probably due to inhibition of membrane binding. Ren al 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, K-A, Of 7.3+/-1.3 mu g ml(-1), and a maximum rate of absorption, V-A,V-Max, of 1.4+/-0.1 mu g min(-1) wer e determined. 4 Iohexol accumulated in kidney tissue, reaching a conce ntration of 2 to 7.5 times the perfusate concentration. In freshly iso lated proximal tubular cells and kidney cortex mitochondria, iohexol r educed the uncoupled respiratory rate at a concentration comparable to the highest tissue concentration found in the IPK. 5 In conclusion, i ohexol is not only filtered by the kidney but also reabsorbed via a sa turable mechanism, which results in tubular accumulation. Intracellula rly sequestered iohexol may affect mitochondrial oxidative metabolism. Our results indicate that iohexol is not a true filtration marker.