Iohexol excretion

Most contrast agents elicit nephrotoxicity because they are primarily excreted by the kidneys. However, when administered in small doses, they constitute a rich source of GFR markers. The two major classes of contrast agents that are finding clinical utility as GFR markers are iodinated aromatic compounds and metal complexes. lodinated aromatics such as iohexol and iothalamate (Fig. 13) are commonly used as contrast agents for computed tomography (GT). They also have pharmacokinetics similar to inulin and hence are useful indicators of renal status [215]. The iodinated molecules used for GFR measurements consist of a triiodo-benzene core and hydrophilic groups to enhance solubility in aqueous medium. 

Low-osmolar media such as iohexol are now preferred for oral use they can still cause some diarrhea, for example in 18 out of 40 cases in one series (SEDA-16, 529). Absorption can be increased if there is mucosal damage in the bowel, such as in Crohn s disease, resulting in delayed excretion but not apparently involving risk (SEDA-18, 441). 

The nonionic contrast media are highly hydrophilic. When given orally, iohexol is absorbed Ifom normal bowel (785). In dogs, approximately 2% of the oral dose is absorbed and excreted in the urine within 6 h, and about 4%of the dose is absorbed and excreted in cats. Using I-labeled iohexol, Mutzel and Speck (267) found intestinal absorption to be about 2% of the intravenous dose given at 60 mg I/mL body weight to male rats. The urinary excretion from the rat was 91.5 3.6% of the administered dose of I-labeled iohexol, and the fecal excretion 6.8 2.7% of the dose 24 h after intravenous injection. In the dog the urine contained 81 9% of the administered dose within 3 h after injection. Total recovery from urinary excretion in the dogduringthe 7 days after injection was 98 4% of the dose and total recovery from fecal excretion was 0.95 0.45%. Healthy volunteers excreted 84% of the dose in urine within 4 h and 100% of the dose within 24 h after intravenous injection at the rate of 25 mL/min of iohexol at a... 

Most authors define CMIN by an increase of serum creatinine of more than 1 mg/ dl 2-3 days after CM exposure. Other reasons for an acute deterioration of renal function have to be excluded. Some investigators even believe that a lower increase of serum creatinine (0.5 mg/ dl 2-4 days after CM) also should be classified as CMIN. It would also be prudent to look for a fall of GFR (general >25% from basehne) with more sensitive methods (i.e. inuhn clearance, iothahnate clearance, iohexol clearance [7. Next to changes in GFR or serum creatinine levels an increase in urinary enzyme excretion seems to also be a sensitive marker of tubular damage after CM exposure [7, 8]. However, no conclusive relationship has been demonstrated between the detection of enzymes in urine and the fall in GFR [8-11]. 

The GFR can be estimated by clearance measurements of endogenous or exogenous small molecules (urea, creatinine, 2-MPT, inulin, cystatin C, iohexol, or iodixanol). An ideal marker of GFR should be primarily excreted by the kidneys, freely filtered by the glomerulus, and neither secreted nor reabsorbed by the tubule. It should also be supplied to the plasma at a constant rate and exhibit no or minimal protein binding. If these criteria are met, such as for inulin, the GFR is equivalent to the renal/urinary clearance of the substance, as defined earlier in this chapter. 

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