"Reduction in uncoupled respiration is an indication of loss of respiratory control and a reduction in mitochondrial oxidative metabolism (Cain & Skilleter, 1987), indicating that this low osmolar contrast agent may induce direct tubular cell injury. Similar results were obtained with the high osmolar agent diatrizoate , and it was suggested that mitochondrial Na-K-ATPase was affected (Humes et al., 1987; Porter, 1994). Heyman et al. (1988, 1991) observed mitochondrial swelling and vacuolization after iothalamate administration, mainly in the medullary thick ascending limb. "
[Show abstract][Hide abstract] ABSTRACT: 1. The renal handling of iohexol was examined in the rat isolated perfused kidney (IPK) over a perfusate concentration range of 5-20 micrograms ml-1. 2. At a concentration of 5 micrograms ml-1, a ratio of renal clearance over clearance by glomerular filtration (ClR/GF) of 0.63 +/- 0.06 could be determined. This ratio increased until 1.02 +/- 0.06 at 20 micrograms ml-1, 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 micrograms ml-1, and a maximum rate of absorption, VA,Max, of 1.4 +/- 0.1 micrograms min-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.
British Journal of Pharmacology 10/1996; 119(1):57-64. DOI:10.1111/j.1476-5381.1996.tb15677.x · 4.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Iodixanol (Visipaque, Nycomed Imaging AS, Oslo, Norway), and isotonic, dimeric and non-ionic contrast medium (CM), and iohexol (Omnipaque, Nycomed Imaging AS, Oslo, Norway), a low-osmolar, monomeric and non-ionic contrast medium, were used as glomerular filtration rate (GFR) markers in patients with severely impaired renal function. Different methods for determining GFR were compared. A total of 16 patients with s-creatinine > 400 mumol/l were enrolled in the study; 8 in each CM group. Serum-iodine was measured, and plasma CM clearance was determined using the Bröchner-Mortensen method, the single-sample method and conventional method. The ratios between the results obtained from the conventional method and each of the two other methods were calculated. These data were plotted against the mean of the pairs compared, and the upper and lower limits of agreement were calculated as the mean ratio +/- 2SD. The comparison showed a high degree of agreement between methods, and the two simpler methods seem to be good alternatives to the conventional method, which gave good estimates of GFR (vs that determined by means of renal 125I-iothalamate clearance) when 24-h blood samples were included. However, slight overestimations of GFR, due to extrarenal excretion of the CM, were observed. In summary, serum clearance of iodixanol, as determined by the Bröchner-Mortensen method or single-sample method seems to be a simple and accurate marker for GFR in patients with severely reduced renal function. The findings obtained with iodixanol were similar to those obtained with iohexol.
European Radiology 01/1996; 6(6):865-71. DOI:10.1007/BF00240692 · 4.01 Impact Factor
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