[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. · 5.07 Impact Factor
[show abstract][hide abstract] ABSTRACT: The authors demonstrate the feasibility of monitoring renal status continuously and noninvasively at a patient's bedside, avoiding both radioactivity and blood and urine samples.
Gadolinium-153-labeled ProHance and a glomerular filtration rate (GFR) standard technetium-99m-DTPA were coadministered to anesthetized normal and nephrectomized rats with their tails hanging in a PC 20 spin analyzer. Blood samples and T1 measurements were collected and analyzed.
Log time plots of 153Gd, 99mTc (from blood samples) and T1 of the rat tails were all linear and parallel. Halftimes were 32 +/- 2, 32 +/- 6, and 32 +/- 6 minutes for the decay of the T1, 153Gd and 99mTc, respectively. The halftime of the nephrectomized animal was 2000 +/- 4000 minutes.
T1 of an appendage remote from the kidneys reflects the concentration of gadolinium in the blood, which is in rapid equilibrium with tissue interstitial space gadolinium. The decay in T1 of the appendage reflects glomerular filtration. Thus, it is feasible to detect changes in renal status at a patient's bedside by monitoring T1 of a finger or wrist using a small, inexpensive magnet.
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